AIDS Manual

for Doctors and Dentists

HONGKONG

AIDSUNIT

香港衛生署愛滋病服務組

July 1995
Hong Kong
 Contents

Foreword 5

Preface 6

How to use this Manual 7

1. Basic science of HIV infection

1.1 Virology and immunology of HIV 9
• Virology of HIV; Immunology of HIV; Vaccine
development and its prospects
1.2 Laboratory tests for HIV 13
· HIV antibody tests; HIV antigen test; Viral
culture and PCR of viral genome; Early
diagnosis of HIV infection

2. Epidemiology, surveillance & control of HIV/AIDS

2.1 Transmission of HIV Infection 16
• The routes of transmission; The risk of
transmission
2.2 T h e H I V / A I D S e p i d e m i c 19
• Global scene; Hong Kong situation
2.3 A I D S p r o g r a m m e & s t r a t e g y i n H o n g K o n g 22
• Historical development; HIV/AIDS education &
health promotion; Surveillance & control; AIDS
care programme

3. Classification, natural history & assessment of HIV

infection
3.1 Classification & natural history of HIV infection 26
• Classification of HIV infection; Primary HIV
infection; Early HIV infection & persistent
generalised lymphadenopathy; Symptomatic HIV
infection & clinical AIDS
3.2 Clinical assessment of HIV-infected patients 34
• Regular clinical evaluation; Clinical markers of
disease progression; Diagnostic approach to
common clinical presentations
3.3 Laboratory assessment of HIV-infected patients 39

1
 • CD4 lymphocyte count; Other virological,
immunological, serological and blood tests

4. Organ/System involvement & special clinical issues of

HIV infection
4.1 Oral, gastrointestinal & hepatic manifestations 42
• Oral problems; Retrosternal discomfort,
dysphagia & odynophagia; Diarrhoea –
gastrointestinal infections & other diseases;
Hepatobiliary diseases
4.2 Respiratory manifestations 47
• Pneumocystis carinii pneumonia; Tuberculosis;
Mycobacterium avium intracellulare; Bacterial,
viral, fungal & parasitic infections; Neoplasia &
inflammatory disorders; Penicillium marneffei
4.3 Neurological manifestations 57
• Meningitis - cryptococcal & other causes; Focal
brain diseases; HIV-related neurological
complications; Neurological diseases due to
cytomegalovirus
4.4 Skin manifestations 64
4.5 Sexually transmitted diseases & HIV 66
• Genital & anorectal herpes; Genital & anorectal
wart; syphilis
4.6 M a l i g n a n c y & H I V 69
• Kaposi's sarcoma; Malignant lymphoma
4.7 O t h e r H I V - r e l a t e d d i s e a s e s 72
• Haematological problems; Endocrine and
metabolic problems; Cardiac, renal &
rheumatological problems
4.8 W o m e n & H I V 77
• Spectrum of HIV disease; Perinatal transmission
of HIV; Other HIV-related issues in pregnancy
4.9 P a e d i a t r i c H I V /A I D S 80
• Clinical manifestations; Laboratory findings and
diagnosis; Management
4.10 Idiopathic CD4+ T-Lymphocytopaenia 85

5. Management of adult HIV Infection

5.1 G e n e r a l m a n a g e m e n t & t r e a t m e n t o f c o m m o n 86
complications

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 • General management - nutrition, lifestyle
modification and others; Treatment and
prophylaxis of common HIV-related diseases
5.2 Antiretroviral therapy 99
• Zidovudine; Didanosine & zalcitabine; Other
antiretroviral agents; Combination therapy;
Current strategy and future direction;
Recommended dosages, monitoring and common
side effects of registered antiretrovirals in Hong
Kong

6. Primary care & psychosocial suppo r t o f H I V / A I D S

6.1 HIV/AIDS counselling and support 107
• Pre-test counselling; Post-test counselling of
negative result; Counselling of people with
positive result; Follow-up psychosocial support
6.2 Confidentialit y 110
6.3 P r i m a r y c a r e o f H I V / A I D S 111
• Professional responsibility to care; Nursing care;
Role of primary care physicians

7. HIV transmission in health care setting

7.1 Introduction 114
7.2 Recommended guidelines and practices relating to 115
prevention of HIV transmission in health care settings
• Precautions for general care; Precautions for
invasive procedures; Precautions for dialysis;
Precautions for endoscopy; Precautions for
dental surgery; Precautions in clinical
laboratories; Precautions for handling and
disposal of dead bodies
7.3 Occupational exposure to HIV 125
• Risk and perspective of HIV transmission in
health care setting; Management of occupational
exposure to HIV
7.4 HIV infection and the health care workers - 128
recommended guidelines

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Appendix I-A: Global AIDS statistics 132
Appendix I-B : Cumulative HIV/AIDS statistics in 133
Hong Kong
Appendix II : Organizational structure of Hong Kong's 134
AIDS programme
Appendix III : Services provided by the AIDS Unit, 135
Department of Health
Appendix IV : Classification for HIV Infection and 138
surveillance case definition for AIDS in
adolescents and adults in Hong Kong
(1995)
Appendix V : Classification system for HIV infection in 140
children less than 13 years of age in Hong
Kong (1995)
Appendix VI : List of locally-prepared documents on 144
HIV/AIDS
Appendix VII: Ethical Guidelin e s o n A I D S b y t h e 147
HKMA/BMA Joint Ethics Advisory
Committee
Appendix VIII: Disinfection procedures to prevent 149
transmission of HIV in health care
settings
Appendix IX: List of infectious diseases requiring special 152
dispo sal procedures for dead bodies
Appendix X : Advice to staff of funeral parlours and 153
relatives on the safe handling of dead
bodies with infectious diseases
Appendix XI : Useful telephone numbers 154
Appendix XII: Abbreviations & Glossary 156
Appendix XIII: Suggested general readings 159
Appendix XIV: HIV/AIDS report form 160

Figure 1: Simplified basic structure of HIV 162

Figure 2: Simplified serological profile of HIV 162
Infection
Figure 3: Route of transmission of reporte d HIV 163
cases in Hong Kong (1984 - June 1995)
Figure 4: Estimated and projected annual AIDS cases 163
in Hong Kong according to different HIV
scenarios

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 Foreword

The AIDS Unit of the Department of Health is to be congratulated for

publishing this manual on AIDS for the information of health care workers in Hong
Kong.

The average local doctor or dentist has only a very limited knowledge about
this disease and there is hardly any published text on this subject that is suitable for
the health care worker in Hong Kong settings. We first got some idea about AIDS,
the disease, the virus, its management and prevention in 1987 when the AIDS
Counselling Service of the Medical & Health Department produced its "Information
on AIDS for Doctors and Dentists" which was subsequently reviewed in 1992.

The publication of this AIDS manual aptly replaces the two previous volumes.
It sets out systematically the updated information on the disease and the virus, the
clinical picture and management protocol. Especially important is the inclusion of
recommended guidelines for prevention of transmission in clinical practice and for
the first time recommended guidelines for the infected health care worker as
formulated by the Advisory Council on AIDS.

A s t he number of HIV infected individuals and AIDS patients is increasing as

expected, many doctors and dentists will encounter this condition sooner or later.
Every health care worker should possess a basic knowledge about AIDS. This
Manual provides this basic and necessary knowledge. Everyone of us should be
familiar with the recommended guidelines mentioned above.

Dr. Lee Kin Hung

President
The Hong Kong Medical Association

5
 Preface

The HIV epidemic in Hong Kong is now in its second decade. Although there
has not been any explosive increase in the incidence of the infection, reported
statistics has recorded a steady rise in the number of cases. It is reasonable to
project that more HIV-infected patients will be encountered in the future, requiring
more input from medical and social services personnel. Health care providers who
have not managed HIV/AIDS patients before should expect to face HIV positive
patients in the coming years.

Against this background, resource manuals are indispensable in preparing

medical professionals in this AIDS era. This manual is prepared as a continuation of
the previous two editions of “ Information on AIDS for Doctors and Dentists ” .
Recent advances in the field of HIV/AIDS have necessitated major reform in the
content and format of the materials presented in this Manual. In compiling this
Manual, we have been much encouraged and supported by staff and patients
around us. We thank Dr. Lee Kin Hung, president of the Hong Kong Medical
Association for his comments and the foreword. We also thank Professor James
Chin for contributing Figure 3, Miss Ng Wai Man for her skillful secretarial support,
Miss Frances Leung for proof-reading the script, and all our patients for prompting
us to come up with the publication.

Finally, we welcome feedback and comments. Your input would be crucial in

helping us improve this Manual when the next edition is published in another few
y e a r s ’ time.

Dr. KH Wong
Dr. SS Lee

6
 How to use this Manual

The Manual is organised into seven chapters and an extensive appendix

section.

Chapter one covers the basic scientific aspects of HIV infection.

Understanding of the virus helps one appreciate its medical complications. Tests for
the infection are covered, which are keys to diagnosis and public health
surveillance. Approach to the establishment of a positive HIV result is discussed.

Chapter 2 depicts the dimension of the HIV epidemic, both globally and locally.
AIDS programme and strategy development in Hong Kong is introduced, as are its
components - prevention, surveillance and care of people with HIV/AIDS. An
overview of the local response to the disease can be grabbed. It would, however, be
necessary to refer to the local document “ S t r a t e g i e s f o r A I D S p r e v e n t i o n , c a r e
a n d c o n t r o l i n H o n g K o n g ” published by the Advisory Council on AIDS for
greater details if necessary.

Chapter 3 to 4 deals with the clinical profile of HIV/AIDS. A general account

of the natural history and common occurrences at different stages of HIV disease
is presented in chapter 3. Clinical and immunologic assessment and recommended
schedule for follow-up of HIV-infected patients are outlined. Diagnostic approach
to common clinical presentations of HIV disease is also included. Chapter 4 deals
with individual organ or system involvement in greater detail. Readers can obtain
summarised information on important medical complications in this chapter, which
may be most relevant for physicians taking care of HIV/AIDS patients, either
currently or in the future. Broader and in-depth coverage are given on the more
commonly affected sites i.e. gastrointestinal, respiratory and neurological systems.
Specific clinical issues, e.g. women and paediatric infection are also highlighted.

C h a p t e r 5 a n d 6 a r e c o n c e r n e d w i t h m a n a g e m ent. Chapter 5 covers the

general management plan, treatment and prophylaxis of common complications, and
antiretroviral therapy for HIV infection. Management of specific diseases are
presented in table format, for easy reference. Recommendations on the use of
antiviral drugs that are available in Hong Kong are given. Not underweighing the
importance of psychosocial support in the overall care of patients infected with
HIV, chapter 6 spells out HIV/AIDS counselling and support in greater detail. Also,
the role of primary care physicians in the overall care and control of the infection is
described in the same chapter.

Chapter 7 is prepared to highlight HIV/AIDS in health care setting. What is

the relevance of HIV infection in health care setting? How can we prevent its

7
transmission? What should be done in case of occupational exposure? How should
we respond to the issue of HIV infection and health care workers?. Colleagues can
find information relevant to their professional practice.

The appendix sectio n is a rich source of reference materials. Guidelines,

protocols, updated statistics, sources of advice, list of publications are presented in
this iscellaneous” section. Readers are welcome to obtain copies of the relevant
documents from the AIDS Unit of the Department of Health.

This Manual is meant to be a comprehensive source of reference, but it is by

no means exhaustive. It is written with the aim of serving as a general reference
manual, in an attempt to suit more readers. Some parts of the contents may be in
excess of what some readers expect while others may be insufficient. Colleagues
are urged to refer to standard texts and references for fine details if they are
desirable. We hope that this Manual can achieve the aim of helping local colleagues
in contributing their expertise towards better control of the HIV epidemic and care
of infected people in Hong Kong.

AIDS Unit
Department of Health

8
 1. BASIC SCIENCE OF HIV INFECTION

1.1 Virology and immunology of HIV

The virus causing acquired immunodeficiency syndrome (AIDS) in human being was
first discovered in 1983, which was then called lymphadenopathy associated virus (LAV),
human T-lymphotrophic virus type III (HTLV-III) or AIDS-related virus (ARV). The name
human immunodeficiency virus (HIV), now widely used, was adopted by an international
committee subsequently formed for its nomenclature. We actually refer to HIV type 1 (HIV-1)
in most of the instances when using the term HIV, as there is another serotype - HIV type 2
(HIV-2), which was discovered in 1986. HIV-2 can cause the same spectrum of diseases,
including AIDS, as HIV-1, although it is considered less virulent than HIV-1. HIV-1 was
responsible for most of the infections of the epidemic worldwide whereas HIV-2 is mostly
prevalent in West Africa, though also found in other places. In Hong Kong, one case of
HIV-2 infection has been reported so far.

Virology of HIV

HIV belongs to the subfamily of

lentivirus. It is a retrovirus, characterised by
Major cell types infected by the possession of reverse transcriptase
HIV (RT), an enzyme which converts viral RNA
* CD4 (T4, T helper) cell to DNA. The basic structure of HIV consists
* monocyte of an envelope and a core (Fig 1). The lipid
* macrophage membrane of the envelope is surrounded by
* follicular dendritic cell an outer membrane protein (gp120) which is
* Langerhans' cell bound to the virus by the transmembrane
* microglial cell of brain protein (gp41). Because of the lipid
* transformed B lymphocyte membrane, HIV is very fragile and is easily
destroyed by heat and dryness. The core,
on the other hand, is composed of a protein
(p24), RNA, and RT. Outer protein enables
the virus to attach to the functionally
important cell surface marker on CD4
lymphocyte, its most important target cell.

After entry into the cell, RT copies the RNA to proviral DNA within activated
lymphocyte, which is then inserted into the host genome and subsequently replicates with
it. This contributes to the chronic latent nature of HIV infection and makes the virus
extremely difficult to eradicate. Genes on the viral RNA codes for all the viral proteins; more
important ones include the g a g gene for core protein, pol gene for polymerase or RT and

9
other enzymes, and env gene for envelope proteins. There are several other unique genes for
HIV, for instance, the t a t a n d rev genes which are important for viral replication. Based on
the variance in the g a g and env sequences, at least 8 subtypes (termed A-H) of HIV-1 have
been isolated. The recent discovery of subtype O from patients of Cameroonian origins have
caused much public concern as it may escape detection by conventional assays. The
genomic organisation (40-45% homology) and function of gene products of HIV-2 are similar
to HIV-1. However, its nucleotide sequence is more similar to simian immmunodeficiency
virus (SIV) rather than HIV-1. SIV is found in some African monkey species but the chronic
infection is largely asymptomatic.

Some other cell types can also be infected by HIV, e.g. monocytes, macrophages,
follicular dendritic cells, Langerhans' cells and glial cells of brain. In fact, macrophages and
dendritic follicular cells are the major reservoirs for HIV replication. HIV is usually only
found in small concentration in plasma and T lymphocytes during the asymptomatic period.
As disease progresses, the concentration increases. Also, the viral phenotype may change
to the syncytium inducing (SI) strains which induce T cells to form syncytia and kill the cells
rapidly.

Immunology of HIV

HIV infection characteristically results

in progressive depletion of CD4 cells, an
Possible mechanisms of HIV- important component of the immune system.
induced immunosuppression Apart from direct killing by the virus, host
* direct killing of CD4 cell (through cells are also destroyed by autoimmune
viral replication within or mechanisms triggered by viral proteins. In
syncytium formation) addition, HIV products can suppress CD4
* HIV products suppress T cell cell function. The phenomenon may
function however be partially beneficial as CD4
* autoantibodies directed against activation is associated with more viral
antigens on immune cells replication and faster cell death. Neutralising
* HIV infects macrophage and affects antibodies at time of HIV infection are weak
its function and do not limit the progress of the
* reduced humoral immunity due to infection. Instead, the CD8 (cytotoxic) T cell
lack of help from T cell response may be more important in the initial
* diversion of cytokines for the control of viral replication. The decline in its
expression and replication of HIV function in later stage of HIV infection has
* diminished HIV-specific cytolytic been found to correlate with disease
T cell activity progression. The loss of TH-1 cytokines,
such as interferon γ and interleukin-2,
through switching to TH-2 cell response, is
one reason for the decrease in cytotoxic
function. Some cytokines, for example,
t u m o u r n e c r o s i s f a c t o r α ( T N F α) a n d T N F β,
increase viral replication directly. In addition
to being a reservoir for HIV, the function of
macrophage as an antigen-presenting cell is

10
 hampered by the virus, and it transfers the
virus to other CD4 cells. There is a great
variety of interaction between HIV and
different components of immune system.
Knowledge of these immune changes and
the immunopathogenesis of HIV is central to
the development of immunomodulatory or
vaccine therapy for the infection.

Vaccine development and its prospects

The development of vaccine against

HIV has been hampered by several
Biological problems in HIV virological constraints. Firstly, it is largely
vaccine development unknown whether protection provided by a
* enormous HIVantigenic variation single agent against a specific strain of HIV
* ability of virus to transmit to can offer similar protection against the
other cell by fusion diverse viral strains originating from rapid
* lack of good animal model mutation. Secondly, it is not known to what
extent a vaccine can have sustained
protection. Other unknowns and
controversies are: whether systemic
immunity can protect against sexual
transmission through mucosal exposure;
whether protection against free virus means
the same for cell-associated virus
transmission. Furthermore, there is the lack
of a suitable animal model which also
manifests an AIDS-like disease with HIV
infection. So far, reference has been taken
from the animal model of other
immunodeficiency virus e.g. SIV, in
developing vaccine for HIV infection in
human being.

Current vaccine development focusses on the use of HIV proteins and peptides as
vectors, development of recombinant proteins, as well as the application of traditional
approach with whole live attenuated or killed virus as immunogens. Recent studies
suggested that protection may be offered by stimulating HIV-specific cell-mediated
immunity, or the functioning of both cytotoxic T lymphocytes and neutralising antibodies,
rather than by antibodies alone (more research done in the past). This area will be the focus
of basic science research in the future. Antigens from conserved region of viral genome has
been used to overcome the problem of diversity of viral strains. For optimal effect, a cocktail
of multiple viral antigens may have to be used in combination. However,

11
potential problems, e.g. antagonism of different antigens and recognition of all the antigens
by body's immunological mechanisms, have to be tackled.

Besides the issue of immunogenicity, the safety and efficacy of the candidate vaccines
have to be tested in clinical studies. The difficulty of implementing any large scale, good
quality human trials cannot be overcome without concerted efforts, good planning and
international co-operation. Phase III trials for HIV vaccine is unlikely to be underway in the
near future, in view of the technical problems anticipated. On the other hand, therapeutic
vaccines may boost the beneficial immune response to HIV. It may, therefore, have a role for
those already infected with the virus in significantly reducing viral burden, slowing disease
progression and possibly minimising risk of transmission. Also, in short of a highly effective
vaccine, even one with only partial efficacy may be invaluable in places with high
prevalence of HIV infection. Of note, however, is that even when a safe and effective
vaccine is available soon - which is very unlikely if not impossible - its value in curbing the
spread of the HIV epidemic will still be limited by its accessibility and affordability. This
underscores the importance of sustained efforts and commitment in strengthening the global
HIV prevention programmes.

12
 1.2 Laboratory tests for HIV

The diagnosis of HIV infection is made by means of laboratory tests, amongst which
HIV antibody test is the most widely used one. The antibody test is also useful in providing
epidemiological information on the prevalence and incidence of HIV infection in a
community, as well as safeguarding blood and blood products. In some circumstances,
however, other tests for HIV such as the detection of HIV p24 antigen, the virus itself or
viral genetic material are indicated. A simplified version of the serological profile of HIV
infection is shown in Fig. 2.

HIV antibody tests

The detection of specific antibodies

* Screening test by ELISA (non-protective) produced by the body in
* Confirmatory test by Western Blot response to HIV is used as evidence of
infection. In routine laboratory practice, it is
(approach used in Hong Kong) composed of (i) a screening assay (usually
by ELISA) and (ii) a confirmatory test
(usually the Western Blot). ELISA stands
for enzyme-linked immunosorbent assay.
Usually, the test serum is added to a plate
coated with HIV protein, which then binds
to the protein if HIV antibody is present.
After incubation and washing, an enzyme-
linked anti-human antibody is added,
followed by an enzyme substrate to produce
the colour change of a positive result. At
present, numerous commercial kits, with
some variation in techniques used, are
available. Other less commonly used
screening methods include particle
agglutination test and dot immunoassay.

Lately, kits for screening both HIV-1 and HIV-2 infection have become available, by
using antigens from both viruses. The screening assays are generally very accurate, with
sensitivity and specificity rates of close to or over 99%. However, their predictive values
depend also on the prevalence of HIV infection in the population tested. For low
seroprevalence populations like Hong Kong, many false positive results may be detected
relative to the identification of truly infected individuals. Testing for HIV antibody has the
advantage that when serum is unavailable in certain settings, saliva or urine samples can be
used alternatively, particularly for the purpose of epidemiological surveillance.

13
 It should be noted that a positive screening (ELISA) result needs to be confirmed.
Western Blot (WB) test is the most commonly used confirmatory test in the local setting.
WB looks for antibody responses to specific proteins of HIV, which were separated
electrophoretically. All HIV positive results issued by the Virus Unit of the Department of
Health are being confirmed by supplemental test. When interpreting WB results, it is
recommended to follow the criteria set by the Centers for Disease Control and Prevention
(CDC) in USA, i.e. a test is considered positive if any two of p24, gp41 or gp120 bands are
present. A partial response with some reaction but not meeting the criteria for positivity is
called "indeterminate result". This may occur in early phase of HIV infection, in which case a
positive result is usually obtained upon repeating the test. Partial responses may represent
non-specific cross-reactions. People with persistently indeterminate results for six months or
more may be considered negative for the infection, if they do not have definite risk factors or
HIV-related symptoms.

HIV antibody tests have limitations

during the early phase of infection when the
antibody is not yet present at detectable
Limitations of HIV antibody level. This w i n d o w p e r i o d may last for as
Tests long as three months because of technical
* inaccurate during the window constraints. The HIV antibody test is most
period between HIV infection and useful when performed in context of
seroconversion (may take 3 counselling and in combination with
months) knowledge of potential exposure to HIV as
* the level of some antibodies e.g well as one's clinical status. Given the
anti-p24 may fall to undetectable enormous potential medical and
level in terminal stage psychosocial consequences of being
* false positive and false negative diagnosed HIV positive, the quality of HIV
results antibody tests (both screening and
* unable to diagnose perinatal HIV confirmatory) should always be ensured. In
infection unless test is positive Hong Kong, HIV antibody test is available
beyond 18 months of age in both the public and private sector. An
external quality assessment programme on
this test is regularly conducted by the
Department of Health's Virus Unit under the
auspices of the Hong Kong Medical
Technology Association. The guidelines
HIV antibody testing - recommended
measures to generate quality results was
established by the Scientific Committee on
AIDS in 1994 to assist laboratories in
improving the quality of performed tests
(Appendix VI). Free confirmatory tests are
also offered by the Virus Unit to samples
sent in by other local laboratories if they
have been screened positive by a
preliminary testing system.

14
HIV antigen test

T he use of HIV p24 core antigen detection to diagnose HIV infection is limited by the
unsatisfactory sensitivity of the assays and unavailability in routine laboratories (because
of the cost) to date. Nevertheless, the test may still be diagnostically useful at the time of
seroconversion and for infants born to HIV positive mother. Also, it serves as a prognostic
marker for HIV disease progression towards a later stage of the infection. An ELISA-based
antigen-capture technique is usually used to detect free antigen in excess of antibody to
p24.

Viral culture and PCR of viral genome

Direct detection of HIV in plasma by culture is insensitive and time-consuming,

although it is considered the gold standard for diagnosing HIV infection because of its
specificity. This method is primarily a research tool. Polymerase chain reaction (PCR)
involves the enzymatic amplification of minute amounts of proviral DNA or viral RNA to a
detectable level. It is highly sensitive and useful for resolving disparate antibody test results
and diagnosing infection in infants. False positive results may, however, result from
carryover of contaminated specimens. At times, false negative results may also occur. All in
all, direct detection of HIV is hampered by its minute quantity in the blood and the
requirement of sophisticated techniques.

Early diagnosis of HIV infection

The development of and subsequent easy availability and widespread use of HIV
antibody tests have made possible early detection of patients infected with HIV. If the test is
used properly, after informed consent and counselling in the case of voluntary testing, it
should be an invaluable procedure for those being tested. For example, although there is
currently no cure for the infection, an early diagnosis will definitely facilitate the monitoring
and management of different stages of HIV disease. With proper intervention, disease
progression is slowed and asymptomatic phase prolonged. Many studies have confirmed
the association between late presentation and poorer patient survival. Early detection of
HIV-infected people is also beneficial from the public health angle as further spread of the
virus can be minimised. Notwithstanding these advantages, possible psychosocial impacts
and other consequences to the tested persons, and more so of the positive subjects, should
always be considered (section 6.1) when the test is performed.

15
 2. EPIDEMIOLOGY, SURVEILLANCE & CONTROL
OF HIV/AIDS

2.1 Transmission of HIV infection

The routes of transmission

For HIV transmission to occur, there

Prerequisites for transmission m u s t b e a significant inoculum of viable
of HIV infectious virus a n d a p o r t a l o f e n t r y into
1. significant viral inoculum the susceptible p e r s o n. Three modes of
2. intact infectious viruses transmission have been documented: (1)
3. correct portal of entry into the sexual transmission, (2) blood-borne
susceptible recipient transmission, and (3) perinatal transmission.
The risk of infection depends on the stage
of HIV infection, being highest at
seroconversion and late stage, when the
viral titre is the highest. Both homosexual
and heterosexual contacts can result in
transmission, often through mucosal
exposure to the virus. Dehiscence in the
integrity of mucosal surface, such as ulcers
or inflammation from sexually transmitted
diseases, frequently facilitates HIV
transmission. On the other hand, proper and
consistent use of condom can significantly
reduce the risk of transmission, as
supported by epidemiological and
experimental evidences.

The acquisition of HIV via blood-borne route occurs in situations like transfusion of
HIV-contaminated blood or blood products, sharing of contaminated needles or syringes in
injecting drug users, and through needle-stick injury in health care setting. On a global
scale, needle sharing among drug users constitutes the most important channel for its
spread through contaminated blood. Perinatal transmission, also called vertical transmission,
is the passing on of infection from a mother to her infant. This can happen before and during
birth, or through breast-feeding.

Casual contact in social setting, such as hand-shaking, sharing equipment or toilet,

eating together, sneezing, hugging, and social kissing, cannot transmit HIV. There is also no

16
evidence to suggest transmission of HIV by mosquito bites. Several instances of household
transmission have been reported recently - via blood-borne contact. However, interpretation
of these rare, isolated events has to be put into the correct perspective against the global
HIV epidemic. Into the second decade of the epidemic, such occurrence actually provides
the best epidemiological proof for the three usual documented modes of HIV transmission.

The risk of transmission

The specific modes of HIV transmission carry the implication that there are behaviours
which put people at risk of infection. This is supported by evidence that most of the known
infections are sexually acquired, or are results of intravenous drug use (via sharing of
needle).

The homosexual community has

Sexual transmission of HIV often been referred as a high risk group for
* depends on sex partners and HIV infection. Biologically, sexual
behaviours rather than sexual transmission o f H I V i s d i r e c t l y r e l a t e d t o t h e
inclination practice of high risk behaviours, notably
* the risk is higher with unprotected that of multiple partners and unprotected
penetrative sex, especially anal penetrative intercourse, rather than to
sex homosexuality or sexual inclination per se.
* higher risk in the presence of Anal sex - which can occur with
sexually transmitted diseases,e.g. homosexuals as well as heterosexuals or
syphilis and gonorrhoea bisexuals - does carry a higher risk of HIV
transmission owing to its inherent traumatic
nature. Another important risk factor is the
presence of sexually transmitted diseases
(STD), which may occur irrespective of one's
sexual inclination. Epidemiologically, it is
true that a major proportion of HIV-infected
people in some places is homosexuals. This
pattern is, however, changing in all parts of
the world - there is a great potential for major
spread within the heterosexual population
because of its big size, though its
prevalence might still remain high in certain
homosexual communities for historical
reasons. The prevention of sexual
transmission of HIV therefore rests on the
reduction of number of sexual partners, and
protected sex to avoid exchange of body
fluids during sexual intercourse, irrespective
of one's sexual inclination.

17
 Intravenous drug use i s a n o t h e r i m p o r t a n t f o r m o f h i g h r i s k b e h a v i o u r c o n t r i b u t i n g
to the spread of HIV infection. Although the average risk of HIV transmission via needle
sharing is not high, spread among drug users can explode once the virus enters a
community with high frequency of needle or syringe sharing. Infected drug users can also
play a crucial role in perpetuating HIV to other communities through sexual and vertical
transmission. Substance abuse and HIV infection have been described in the USA as the
'twin epidemic', literally illustrating the epidemiological significance of the intertwining
problems. Prevention of HIV spread among drug users can be achieved by the
encouragement and ensurance of use of new injection equipment and avoidance of sharing
of needles and syringes (harm reduction). The strategy should be in place together with the
common goal of drug detoxification and rehabilitation.

T h e r i s k o f perinatal HIV transmission v a r i e s w i t h t h e m a t e r n a l H I V s t a t u s , s t a g e

of disease, accessibility to health care facilities as well as other yet undefined factors. The
overall risk of transmission from an infected mother to the newborn ranges from 15% to 40%,
generally being higher in developing than developed countries. Prevention of perinatal
infection depends on the identification of HIV positive women before or during pregnancy,
refrainment from or discontinuation of pregnancy, and possibly medical intervention during
pregnancy and delivery (section 4.8). However, it has to be stressed that the mother's
decision is overriding, after appropriate counselling and psychosocial support. Also, for the
maximum benefit of HIV-infected babies, early HIV diagnosis, regular monitoring and prompt
treatment should be offered as necessary and feasible.

Haemophilia i s a r a r e h e r e d i t a r y c o n d i t i o n c h a r a c t e r i s e d b y t h e d e f i c i e n c y o f
certain clotting factors, of which Haemophilia A (or Factor VIII deficiency, a sex-linked
genetic disease) is the commonest. Clotting factor replacemnent is the standard treatment for
haemophilia patients, especially those suffering from severe deficiency. Worldwide, vast
majority of HIV infection among haemophiliacs occurred in the late seventies / early eighties,
when safer blood products were not available and HIV-contaminated ones were
unknowingly given to the patients. HIV-infected haemophiliacs suffer from the
complications and stigmatisations associated with both conditions.

Blood transfusion m a y a l s o r e s u l t i n H I V i n f e c t i o n i f c o n t a m i n a t e d b l o o d i s u s e d .
With the implementation of HIV screening, the chance of such occurrence has become
remote. In Hong Kong, universal screening of donor blood has been undertaken by the
Hong Kong Red Cross Blood Transfusion Service since August 1985. There is, however,
still the minimal chance of HIV infection occurring if an infected donor gives blood during
the 'window period' before HIV antibody becomes detectable (section 1.2). People who have
practised high risk behaviours (sexual or drug-taking) should be advised to refrain from
donation.

18
 2.2 The HIV/AIDS epidemic

Since the report of the first AIDS cases

in the USA in 1981, its causative agent (later
Problems with reported data discovered and called HIV) has been
* underdiagnosis spreading relentlessly worldwide. The
* underreporting understanding of the epidemiology of the
* time lag in reporting infection was made possible through
reporting of HIV infection and AIDS cases,
together with estimation and projection of
the actual dimension of the epidemic by
various methods, including mathematical
modelling. In this context, international
collaboration has become an essential
component of the AIDS control programme
on the global level, through the coordination
of the World Health Organization (WHO). In
this regard, the Global Programme on AIDS
was established under WHO to monitor and
advise on the prevention of HIV
transmission. Accuracy of reported data
from different countries depends on the
system adopted, completeness of case
reporting and the degree of delay required.
The reporting system has, therefore, limited
usefulness in advancing our understanding
of the epidemiological pattern both locally
and globally.

Global scene

As of the end of June 1995, a total of

1169811 AIDS cases worldwide have been
WHO estimations reported to the WHO (Appendix I-A). Even
* 18.5 million adult HIV cases though the greatest number of reported
* 1.5 million infected children cases comes from the Americas, it is
* > 4.5 million AIDS cases believed that Africa actually has the highest
* 30-40 million HIV infections by the number of cumulative AIDS cases in the
year 2000 world. The WHO has estimated that over 4.5
million HIV-infected people have developed
AIDS since the epidemic began.

19
 The true dimension of HIV infection is even
more difficult to be ascertained, because of
its asymptomatic nature, the long incubation
period from infection to overt disease, and
Global HIV cases by exposure the varied accessibility to HIV testings. The
category WHO has estimated that there are now a
* heterosexual : 60-70% cumulative 18 million adults infected with
* homosexual : 5-10% HIV, the greatest proportion being in
* injecting drug use : 5-10% Subsaharan Africa (over 11 million),
* perinatal : 5-10% followed by South East Asia (3.5 million),
* blood/blood product transfusion : North America (1.1 million), Latin America (2
3-5% million), Europe (about 0.5 million) and
Australia (over 25 thousand). No place is or
will be immune of HIV infection, and the
fastest growth of the epidemic has recently
been noted in countries of South East Asia,
such as Thailand, India and Myanmar.
About 1.5 million children have been
infected by HIV thus far. By the year 2000,
the WHO projects that as many as 30-40
million people might have become infected
by the virus, with 90% in the developing
countries. As a result, more than 10 million
children will be orphaned by AIDS.

Globally, sexual contacts accounted for 70-80% of all infections, with the majority
being heterosexually (60-70%) rather than homosexually (5-10%) acquired. The importance
of each risk factor, however, varies from country to country. For example, HIV spreads
predominantly by heterosexual contacts in Africa, with a male to female cases ratio of about
1:1. In North America, Europe and Australia, majority of the known cases were related to
homosexual activity. There is evidence, however, that the epidemiological pattern is
changing with increasing incidence of heterosexual transmission, and more women are
becoming infected recently. Heterosexual contact is also the main route of HIV transmission
in South East Asia.

20
Hong Kong situation

The first case of HIV infection in Hong

Kong was reported in late 1984. By June
1995, a cumulated 573 cases have been
reported to the Department of Health, of
which 148 have progressed to AIDS
(Appendix I-B). Yet, based on
Features of HIV epidemic in epidemiological analyses undertaken
Hong Kong recently, as estimated 3000 HIV infections
* increasing heterosexual have actually occurred and 250 persons
transmission have already progressed to AIDS.
* increasing no. of women infected
* low infection rate among drug users In the early years of the epidemic in
* steady growth in total cases Hong Kong, most of the reported infection
were among the homosexuals and the
haemophiliacs. There was no new reported
infection through transfusion of
contaminated blood or blood products
occurring after August 1985. Reports of HIV
infection in the homosexual and bisexual
community continued, but the actual number
of newly diagnosed cases has been
surpassed by heterosexuals since 1991.
There are now almost three to four times
more heterosexually acquired new infection
reported than homosexual cases, and the
gap is widening (Fig 3).

To date, only 10 % of the reported HIV infection have occurred in women. The rate of
increase of HIV infection in females was, however, particularly rapid in the past two years.
With the increasing trend of heterosexual transmission, it is likely that more women will
become infected by the virus. Locally, two cases of perinatal transmission has been
reported, the first case in mid-1994. Again, more similar cases would be expected in parallel
with the rising trend of heterosexual transmission and of women becoming infected with
HIV.

The prevalence of HIV infection among drug users in Hong Kong has remained low, as
evidenced by the low reported number (2% of the total HIV cases) and surveillance data
collected through unlinked anonymous screening.

Overall, cumulative HIV infection has increased by 20% - 30% per year in the last
couples of years. According to the projection made in 1994, the cumulative infection by the
year 2000 may range from 8000 to 12000, depending on its rate of spread. The annual
incidence of clinical AIDS will be about 200-300 in the coming years, rising to 350-450 by
2000 (Fig 4). Even though the HIV prevalence is relatively low (<0.1%) now, it is predicted
that the infection will grow steadily in the coming years. Because of its impact on young
people, AIDS may become the cause of 20% of all deaths between the age of 20 and 49 at
the turn of the century.

21
 2.3 AIDS programme & strategy in Hong Kong

An effective AIDS programme

Aims of AIDS programme addresses not only prevention and control
* prevent HIV transmission of the disease, but also the care of those
* reduce negative impacts of infected. In Hong Kong, the objectives of
HIV/AIDS on the individual and the AIDS programme are:
the society
i. to prevent HIV infection;
ii. to reduce the negative impacts of the
disease on affected individuals and
society;
iii. to reduce societal discrimination and
promote respect for human rights and
dignity;
iv. to develop and strengthen global
solidarity against HIV/AIDS, thereby
advancing the health of all people.

Historical development

Hong Kong's AIDS programme has

Three phases of AIDS programme gone t h r o u g h t h r e e p h a s e s . T h e initial
development in Hong Kong phase s p a n n e d f r o m 1 9 8 4 t o 1 9 8 6 . I t s t a r t e d
1. Initial phase when an Expert Committee on AIDS was
2. Intensification phase established by the then Medical & Health
3. Consolidation phase Department to advise the government on
how to cope with the new disease. A
Scientific Working Group on AIDS was set
up in 1985 to implement, coordinate and
monitor prevention activities. Key
achievements during this period included:
establishing an AIDS counselling clinic and
a hotline, ensuring supply of safe heat-
treated blood products, safeguarding blood
supply through blood-screening by the
Hong Kong Red Cross Blood Transfusion
Service (HKRCBTS), establishing an
HIV/AIDS surveillance system, and
providing the HIV antibody tests to people
at risk of infection.

22
 D u r i n g t h e intensification phase ( 1 9 8 7 - 1 9 8 9 ) , p u b l i c e d u c a t i o n w a s h i g h o n t h e
agenda. A committee on education and publicity on AIDS and a publicity working group
were formed to initiate, implement and coordinate publicity and education programmes.
These were put forth through the aid of various government departments as well as
community organisations. Media publicity was strengthened, with television spots (API)
being produced by the Government Information Service, focussing on various aspects of
HIV/AIDS. The AIDS Counselling and Health Education Service of the Medical & Health
Department was expanded to become an operational arm of the committee, which organised
educational activities targeting various community groups.

T h e t h i r d p h a s e - consolidation - b e g a n f r o m 1 9 9 0 . A c e n t r a l A d v i s o r y C o u n c i l o n
AIDS, appointed by the governor, was established in March 1990. The council has served to
develop AIDS strategy and streamline the operations of Hong Kong's AIDS prevention,
care and control programme. Community participation was encouraged. Both the Hong
Kong AIDS Foundation and the AIDS Concern were formed during this same period. In
early 1993, the AIDS Trust Fund was set up to provide ex-gratia payment to HIV-infected
haemophiliacs and transfusion recipients, and to fund educational and AIDS care projects.
The Advisory Council on AIDS is now underpinned by three committees - Committee on
Education & Publicity on AIDS (CEPAIDS), Scientific Committee on AIDS (SCA), and the
AIDS Services Development Committee (ASDC). Secretarial support is provided by the
Department of Health's Special Preventive Programme. In 1994, the Council published its
policy in a document titled Strategies for AIDS Prevention, Care & Control in Hong Kong .
Services provided to people with HIV/AIDS were reviewed; and the HIV surveillance system
was strengthened through the initiation of studies on scenarios and behaviours.

The structure of the existing AIDS programme in Hong Kong is depicted in Appendix
II. Both government departments / policy branches and voluntary agencies participate and
contribute to the overall AIDS programme. The AIDS Unit of the Department of the Health,
operative under the Special Preventive Programme, remains an important operational arm for
initiating and undertaking a good range of AIDS-related activities, and its services are listed
in Appendix III.

HIV/AIDS education & health promotion

In Hong Kong, as is the case in any

Integral components of the country, publicity and education are
HIV prevention programme essential components in the prevention and
* provision of information and control of HIV infection. Provision of correct
education information and education on HIV/AIDS is
* accessible health services crucial for virtually everybody. Different
* supportive social environment approaches and emphases are adopted
and protection of marginalised, when targetting people of different
at risk groups background, including the practice of high
risk behaviours. A positive attitude
towards the infected

23
 patients is promoted, besides educating
people on how to protect themselves from
the infection. It is noted that sustained
avoidance of high risk behaviours cannot be
achieved without a supportive social
environment, e.g. public perception of safer
sex and the use of condoms. Relevant AIDS
education programmes have to be
undertaken consistently, coordinated and
integrated with other health and social
activities as necessary.

Prevention of sexual transmission is indisputably the most important component of the

overall AIDS prevention strategy. There should be (i) provision of information and
education to bring about behavioural modification, (ii) provision of early detection and
treatment of sexually transmitted diseases, and (iii) opportunities for developing programmes
tailored to meet the needs of various sectors of the community. For instance, methadone
programme and clean syringes should be readily accessible for drug users, as well as quality
(acceptable, prompt diagnosis and treatment) sexually transmitted diseases services for
clients at high risk of sexual transmission of HIV.

Surveillance & control

The WHO defined public health

surveillance as the collection of

HIV antibody testing information of sufficient accuracy and

1. voluntary testing completeness regarding the distribution
2. unlinked anonymous screening and spread of infection to be pertinent to
3. screening at blood or organ the design, implementation or monitoring
donation of prevention and control programmes and
activities. HIV infection, in view of its
complexities and considerable social
implications, is a superb example of why a
good surveillance system is indispensable
for the purpose of strategic planning. In
conducting surveillance activities, it is
prudent not only to maximise the likelihood
of obtaining useful and accurate information
but also to minimise the likelihood of
adverse consequences. The HIV/AIDS
surveillance system in Hong Kong is made
up of three arms: (i) voluntary reporting
system; (ii) surveillance among selected
groups; and (iii) unlinked anonymous
screening (UAS).

24
 Except for UAS, the person tested is and should be counselled and informed of the
testing, and that support services should be available for those detected positive (section
6). UAS is the testing of specimens for markers of infection after elimination (unlinking) of all
personal information from each specimen. International guidelines on undertaking UAS for
public health surveillance of HIV infections were established by the WHO in 1989, and the
system has been adopted in Hong Kong since 1990. UAS has been conducted on neonates,
tuberculosis patients, prisoners as well as drug users.

HIV surveillance is deemed incomplete

HIV surveillance if the related behaviours are not monitored.
1. Infection surveillance by HIV In contrast to defining seroprevalence,
tests behavioural surveillance is the gauging of
2. Behavioural surveillance by the vulnerability for HIV infection of people
monitoring AIDS-related or specific populations. Two aspects of
behaviours AIDS-related risk behaviours are usually
focussed - sexual and drug-taking
behaviours. Through regular monitoring of
the changing pattern of such behaviours,
this complementary activity is especially
useful for the design of appropriate
interventional activities, before HIV
transmission actually occurred.

AIDS care programme

Care and support of people infected by

AIDS care programmes HIV and their families/partners is an integral
* clinical management component of a comprehensive AIDS
* psychosocial support services programme. HIV management encompasses
outpatient treatment, inpatient treatment,
social and support services, counselling,
referrals for specialists' advice, and
coordination of available services. Clinical
management (including treatment and
prophylaxis of complications) is beneficial
in maintaining health, relieving physical
sufferings and delaying disease
progression. Psychosocial support services
should also be available for both the
patients and their close ones. Partnership is
a key element in any successful programme,
and community participation is especially
important in this regard.

25
 3. CLASSIFICATION, NATURAL HISTORY &
ASSESSMENT OF HIV INFECTION

3.1 Classification & natural history of HIV infection

The clinical course of HIV infection is best depicted as a continuum, from acute
infection to the development of AIDS and eventual death. The acute infection may be
subclinical or symptomatic. Afterwards, the disease enters its chronic phase of varying
duration but is usually characterised by the presence of a prolonged period of asymptomatic
infection. Gradually, as the immune system is progressively depleted, the infected patient
begins to experience symptoms arising largely from its complications.

Classification of HIV infection

In view of the wide spectrum of

diseases and range of clinical signs and
HIV classification symptoms associated with HIV infection, the
* provides a standardised way of Centers for Disease Control (CDC) of the
staging and categorising HIV- United States had devised a classification
related morbidity system for adult HIV infection in 1987. At
* reduces confusion and facilitates around the same time, the surveillance case
exchange of disease information definition for AIDS was also formulated. The
* guides the prognosis and therapy CDC classification divided HIV diseases into
of patients four groups: group I was acute HIV
* serves as basis for public health infection, group II was asymptomatic HIV
surveillance to evaluate and design infection, group III was persistent
appropriate health care services generalised lymphadenopathy (PGL), and
group IV referred to a variety of HIV-related
conditions. Group IV was further divided
into subgroups A to E, and encompassed
constitutional diseases, neurological
diseases, secondary infections, cancers and
other unclassified conditions. Though not a
perfect staging system, the original or
adapted form of 1987 CDC HIV classification
system was probably the most widely used
one in the world, and has also been adopted
in Hong Kong. It is important to note that
the different stages of this classification
system are not given in their order of clinical
severity.

26
 In 1993, the CDC revised the classification system (Appendix IV-A) for HIV infection
by incorporating also the CD4 lymphocyte count because of its clinical and prognostic
significance. Staging is therefore made by considering both the clinical condition and the
CD4 level. There are three clinical categories: category A consists of either asymptomatic
HIV infection, PGL or acute infection; c a t e g o r y B refers to symptomatic HIV infection but
not yet clinical AIDS; and category C includes the AIDS-indicator conditions. Similarly,
t h e r e a r e t h r e e c a t e g o r i e s b a s e d o n t h e a b s o l u t e C D 4 c o u n t : c a t e g o r y 1 f o r c o u n t ≥ 500
cells/ul; c a t e g o r y 2 for 200-499 cells/ul; and c a t e g o r y 3 for <200 cells/ul. For both clinical and
CD4 categories, the 'higher' options take precedence. Depending on different combinations
of the two categories, there are nine possibilities of the stages. Further to this revision, the
CDC has also expanded the AIDS surveillance case definition by adding three clinical
c o n d i t i o n s ( Mycobacterium tuberculosis infection of any site - pulmonary or extrapulmonary,
invasive cervical cancer and recurrent pneumonia) to the 1987 list of 23 diseases and also
including the immunological criteria of CD4 count <200/ul or CD4 percentage <14.

The new classification system is primarily intended for the staging of people with
HIV/AIDS in the United States. It provides a framework in enabling clinicians to have a fast
and clear idea about the rough extent of clinical and immunological manifestations of an
HIV-infected patient. The expanded AIDS case definition, especially the CD4 level criteria, is
however not adopted worldwide. This is not surprising as disease pattern varies from place
to place, and so are the requirements for health care provision. For example, tuberculous
infection is highly prevalent in Hong Kong, and it may be difficult to differentiate between
tuberculosis arising from HIV infection or coexistence of the two diseases. On the other
hand, disease like Penicillium marneffei infection occurs not uncommonly in severely
immunosuppressed HIV positive patients in Hong Kong but not in the west. In practice,
Penicillium infection has been included as an AIDS-defining illness by the Department of
Health in Hong Kong. Lastly, the CD4 count enumeration may not be freely available in
some countries, and its inclusion as a diagnostic criterion carries other implications like that
of confidentiality in reporting.

In 1995, the Scientific Committee of the Advisory Council on AIDS formulated its
new classification system for HIV infection and surveillance definition for AIDS in Hong
Kong. The 1993 CDC classification system was recommended for clinical monitoring of
disease. As for surveillance definition, a modified approach has been adopted (Appendix IV-
B). An HIV-infected patient who has either one of the 25 indicator diseases established in
the 1993 CDC surveillance definition or Penicillium marneffei infection is considered as
suffering from AIDS, irrespective of the CD4 count or whether the latter test has been
performed. Of note is that in order for pulmonary TB (with or without involvement of the
drainage lymph nodes) to be treated as an AIDS indicator illness, the patient's CD4 count
must be < 200/ul and/or his CD4% < 14.

27
Primary HIV infection

Acute infection by HIV can be

Clinical features
* recent risk behaviour/activity with
possible exposure to HIV
* acute febrile flu-like illness with
one or more of skin, neurological,
gastrointestinal and systemic
manifestations
subclinical or characterised by a variety of
clinical manifestations. The exact frequency
of symptomatic primary HIV infection is hard
to be ascertained, largely because of the
problem of inadequate clinical suspicion and
thus underdiagnosis. It has been estimated
to occur in 50-70% of patients infected with
HIV. The acute illness typically presents 2 to
4 weeks after exposure to HIV, during which
period there is intense viral replication and a
precipitous fall in the CD4 count. Acute
seroconversion sickness overlaps with the
host's immune response to HIV.

Initially described as a mononucleosis-

Differential diagnosis
like condition, HIV seroconversion illness
Infectious mononucleosis
has been increasingly recognised as a
Cytomegalovirus infection
distinct clinical syndrome. The clinical
Toxoplasmosis
spectrum classically consists of general,
Rubella
dermatopathic, neuropathic and
Syphilis
gastrointestinal features. There is typically
Viral hepatitis
an acute onset of fever, night sweats, sore
Primary herpes simplex infection
throat, myalgia, arthralgia, lethargy and
Influenza and other viral infections
lymphadenopathy. An erythematous, non-
pruritic, maculopapular rash is also common,
frequently starting from face and trunk and
may become generalised. Disseminated
urticaria, rosacea-like rash or vesicular
exanthema are less commonly encountered.
As a neuropathic virus, HIV may infect the
central nervous system and cause aseptic
meningoencephalitis. Peripheral neuropathy,
myelopathy, and Guillain-Barre syndrome
are other less common neurological
manifestations. Gastrointestinal features
include mucocutaneous ulceration of the
gastrointestinal tract, oral or oesophageal

28
 candidiasis, nausea, vomiting and diarrhoea.
In addition, other manifestations such as
aplastic anaemia, hepatitis, pneumocystis
pneumonia with respiratory failure and
rhabdomyolysis may rarely occur. The acute
illness is usually self-limiting and lasts for 1
to 2 weeks. Its association with more rapid
progression to AIDS has been described.
Treatment is basically symptomatic.

Several clinical features may help to

differentiate acute HIV infection from other
viral infections. Diarrhoea and skin rash
occurring in acute HIV infection do not
usually present in infectious mononucleosis
without antibiotic treatment, and
mucocutaneous ulceration is uncommon in
other viral infections except herpes simplex.
A combination of skin and mucosal signs in
a patient with febrile flu-like illness should
alert one to primary HIV infection, if there is
preceding history of high risk behaviours.
Laboratory tests are useful to support and
confirm the diagnosis and exclude other
differential diagnoses. More often than not,
CD4 lymphocyte count is profoundly
Laboratory features reduced temporarily, with a reverse in the
* positive p24 antigenaemia and/or CD4:CD8 ratio. Mild thrombocytopaenia and
HIV antibodies leucopaenia may occur. For HIV-specific
* low CD4 level and reversed tests, p24 antigen is detectable in the blood
CD4 to CD8 ratio in majority of the patients, and before HIV
* mild thrombocytopaenia antibodies show up. When primary HIV
* no evidence of other recent infection is suspected, both HIV antigen and
infections e.g. -ve serology to EBV antibody tests are indicated after
and CMV appropriate counselling, and they should be
repeated as necessary. Early recognition of
seroconversion is important not only in
terms of education against further spread of
HIV, but may also facilitate early
intervention which could potentially
improve the long-term clinical outcome of
HIV disease.

29
Early HIV infection & persistent generalised lymphadenopathy

After acute primary infection, most

Indications for biopsy in HIV patients enter into a stage of asymptomatic
with lymphadenopathy disease which may last for months to years.
* asymmetrical enlargement During this phase, there is minimal signs and
* rapidly growing nodes symptoms except for the possible
* painful nodes occurrence of persistent generalised
* presence of systemic symptoms lymphadenopathy (PGL). PGL is defined as
* presence of visceral e n l a r g e m e n t o f l y m p h n o d e s o f ≥1 c m o v e r
lymphadenopathy two or more non-inguinal sites that lasts for
* suspicion of causes other than PGL more than three months in an HIV positive
patient without other causes. The
lymphadenopathy is characteristically
symmetrical and painless, with the absence
of constitutional symptoms and visceral
lymphadenopathy. Biopsy is not necessary
in the case of a typical presentation, which
usually only shows non-specific reactive
follicular hyperplasia.

The presence of PGL does not appear to adversely influence the prognosis of HIV
disease. Instead, its disappearance may herald progressive lymphopaenia and deterioration
of immune function. It has recently been found that the period of clinical latency of HIV
infection is not parallelled by a viral latency. More sensitive laboratory techniques, notably
the polymerase chain reaction (PCR) and in-situ hybridisation, have shown that there is an
enormous infiltrate of lymphoid organs by HIV, at all stages of the infection. The minimal
viral burden and replication detected in peripheral blood during early HIV disease is sadly
enough not a true reflection of the state of overall HIV replication and host cell destruction.
With time, activated CD4 cells and macrophages that are infected with HIV are progressively
eliminated and free HIV virions are released into the circulation, which in turn encourage
further CD4 cell activation and viral replication. The vicious cycle continues until the
lymphoid system is so depleted that it breaks down and huge amount of virus then enters
the peripheral circulation. Disease progression is generally evident by that time.

30
Symptomatic HIV infection & clinical AIDS

The progressive destruction of

lymphoid cells leads to the development of
HIV constitutional symptoms HIV-related symptoms, which sometimes
Fever may be constitutional. The commonest
Night sweats systemic symptoms are fever, night sweats,
Diarrhoea lethargy, unexplained diarrhoea, and weight
Weight loss loss. These symptoms may be prolonged or
Malaise/lethargy intermittent. Together with PGL and some
abnormal immunological findings, the
constitutional symptoms are, in the absence
of secondary complications, previously
classified under the syndrome called AIDS-
related complex (ARC), a term uncommonly
used nowadays. If the symptoms are so
marked that there is involuntary loss of >
10% of baseline body weight, plus either
diarrhoea or fever lasting at least a month, a
diagnosis of wasting syndrome is made,
which is an AIDS-defining condition.
Management of constitutional illness
includes active exclusion of intercurrent
secondary infections or cancers, antiviral
therapy and also symptomatic treatment, e.g.
antipyrexial and antidiarrhoeal agents.

As immunodeficiency progressively
worsens, the body becomes increasingly
vulnerable to various opportunistic
infections and/or cancers. The infected
patient finally enters the stage classifiable as
AIDS, when he/she suffers from more and
more morbidity and finally mortality. Specific
clinical manifestations of HIV infection
occurring over time are discussed in greater
details in subsequent chapters. The rate of
progression of HIV disease varies
substantially from patient to patient. From
the results of cohort studies of homosexual
men, it is known that about 50% of the
infected patients develop clinical AIDS in 10
years. The cumulative risk increases with
time lapse after acquisition of the infection.
Studies of transfusion-related HIV infection
has suggested a faster rate of
progression. In

31
 contrast, progression in HIV-infected
haemophiliacs is in general thought to be
slower, except for those who are older (age
>35 years ) at time of seroconversion. The
rates of progression of HIV infection in
injecting drug users and women are not
clearly defined. Nonetheless, they are
believed to be similar to patients with other
risk factors of HIV transmission. It is not
known yet whether all HIV-infected persons
will develop AIDS, though this is highly
likely if given adequate time for the disease
to progress. Recent studies suggested that
there was a small sub-group of patients who
could be classified as non-progressors in
view of the stable CD4 counts and absent
clinical complications. The prevalence varied
from cohorts to cohorts, and was likely to be
only about 5% after a period of 7 to 10 years.

Different AIDS-indicator diseases

present at different point of time during the
course of the disease, reflecting their
Spectrum of AIDS-defining occurrence as a function of the underlying
diseases varies with immune function. For example, Kaposi's
* stage of HIV infection sarcoma (KS) usually appears early when
* local prevalence of diseases, the immune system is still relatively intact.
especially endemic infections The spectrum of clinical diseases varies also
* availability of antiviral therapy, with the prevalence of different endemic
prophylaxis and treatment of infections in the locality. Modern advances
complications in medical therapy and management have
somewhat altered the course of HIV disease,
changed the disease pattern and delayed the
onset of clinical AIDS in some patients,
though not to a great extent. For instance,
the incidences of Pneumocystis carinii
pneumonia (PCP) and KS have decreased
while those of Mycobacterium avium
intracellulare (MAI) and cytomegalovirus
(CMV) disease, usually occurring at
advanced immunosuppression, have
increased. It is hoped that in the future,
medical advances can significantly prevent
or delay the onset of HIV-related morbidity
and mortality.

32
 Median survival of patients after AIDS diagnosis has improved over the years, more
so in the developed countries, although the overall outlook is still poor. In places with the
best figures, AIDS patients now survive for a mean of 18 to 24 months. In Hong Kong,
survival of AIDS patients have also improved in recent few years. Possible reasons for the
improved survival are: earlier diagnosis and treatment of life-threatening conditions;
effective prophylaxis of secondary infections especially PCP; advances in antiretroviral
therapy and other forms of treatment. It should be noted, however, that with increasingly
effective prophylaxis of opportunistic infections and potent antiviral therapy, clinical AIDS
may be deferred to the truly terminal stage of HIV infection with complications inamenable to
modern management. The survival time after AIDS may also be affected by the case
definiton of AIDS adopted.

In addition to the length of time after

HIV infection, several other factors have
Possible factors influencing HIV been suggested to affect the progression.
disease progression There are the virus factors like the inoculum
received and pathogenicity of the viral strain

HIV or strains; clinical and immunological status

* inoculum of virus at infection at time of infection; host factors such as
* viral burden changing with time nutritional status and immunological
* virulence of strain e.g syncytium- response to HIV infection. Other infectious
forming phenotypes agents or environmental factors may also
* development of resistance to affect the course. There have been
antiviral drugs laboratory and epidemiological evidences
indicating that herpes simplex infection may

Host be a cofactor for progression to AIDS.

* age at time of infection Certain Mycoplasma strains and cigarette
* immunological response to HIV smoking have also emerged as possible
* antiviral therapy and management cofactors. In addition, opportunistic
of HIV-related complications infections may perpetuate the downhill
course of HIV disease.

Others
* secondary infections as cofactors
* time lapse after infection

33
 3.2 Clinical assessment of HIV-infected patients

T h e c o m p l e x i t y o f p r o b l e m s r e s u l t i n g f r o m H IV i n f e c t i o n d e m a n d s a c o m p r e h e n s i v e
clinical, laboratory and psychosocial assessment to be made for management to be
optimised. This should be implemented throughout the course of the infection, although
emphasis placed on each modality may vary according to the different stages of HIV
disease, as well as the interplay amongst them. Health care professionals and other service-
providers shall be prepared to face the challenge.

Regular clinical evaluation

HIV infection can manifest with a good

Rationale for clinical evaluation variety of clinical signs and symptoms. A
* regular monitoring of HIV status thorough history and physical examination
* allows antiviral therapy and is therefore desirable as recognition of the
prophylaxis for infections to be clinical manifestations can guide the
given when necessary subsequent investigations and management
* allows prompt diagnosis and as appropriate. Symptoms in the early stage
treatment of complications are often constitutional and may need
symptomatic treatment. On the other hand,
[ frequencyof follow-up has to be the most common early signs are

individualised while basing on dermatological and constitutional. At this

recommended schedule] stage of HIV disease, clinicians should look

for abnormalities like lymphadenopathy,
fever, oral and anogenital lesions,
seborrhoeic dermatitis, molluscum
contagiosum, bacterial and fungal skin
infections and provide management
accordingly. During early HIV infection,
when no antiviral therapy is instituted,
patients may be seen every three months or
so unless there are intercurrent problems.
The emphasis should be on the provision of
regular clinical follow-up and laboratory
monitoring of the HIV/immunologic status.

W i t h t i m e , m o r e d i v e r s i f i e d HI V - r e l a t e d s y m p t o m s a n d s i g n s m a y p r e s e n t , a n d t h e s e
should be actively looked for. When the patient is started on antiretroviral therapy or
opportunistic pathogen prophylaxis, they may be seen every 4 to 6 weeks if the condition is
stable, after initial intensive monitoring. The condition may need to be reviewed more
frequently if there is evidence of clinical or immunological deterioration. Obviously, when a
patient is severely immunocompromised or has developed clinical AIDS, he/she requires
more frequent care and attention which, however, have to be individualised and tailored to
one's specific needs.

34
Clinical markers of disease progression

HIV infection is a chronic disease with

Prognostic markers a long asymptomatic phase. In its
fever management, it is useful to look out for
weight loss prognostic markers which may predict
oral candidiasis hastened disease progression. This permits
oral hairy leucoplakia care to be maximised through the delivery of
herpes zoster more informative counselling and early
"aggressive" medical management. Several
clinical and laboratory markers have been
found to be associated with a faster
progression of HIV disease. The clinical
ones include presence of signs and
symptoms like fever or weight loss, and
conditions such as oral candidiasis, oral
hairy leucoplakia and herpes zoster. In
addition, patients with a severe or prolonged
seroconversion sickness have a poorer
prognosis.

Diagnostic approach to common clinical presentations

Several clinical presentations are common in the course of HIV infection e.g. cough
and fever, diarrhoea and neurological problems. The differential diagnoses depend on
individual clinical setting and the stage of HIV disease. Detailed clinical history and
complete physical examinations are clearly a must for making a provisional diagnosis to work
upon; nevertheless, investigations are usually necessary afterwards. The general approach
to some of the common clinical problems associated with HIV/AIDS are outlined below.

35
 Presentation Diagnostic approach

cough and fever Chest X-ray

± dyspnoea * bilateral/diffuse interstitial infiltrate: PCP (may have alveolar infiltrate),
disseminated TB (may be miliary), severe bacterial bronchopneumonia, KS
(may have opacities or streaks), CMV pneumonitis, interstitial pneumonitis
* focal consolidation: bacterial pneumonia, atypical pneumonia,
PCP(uncommon)
* thoracic lymphadenopathy: TB, KS, non-Hodgkin's lymphoma
* pleural effusion: TB, KS, bacterial pneumonia, cryptococcosis
* normal: PCP, KS
Sputum - routine, induced (for PCP, TB)
*gram stain, microscopy (including AFB), culture (also for mycobacteria
and fungus), and cytology; repeat as necesary
Oxygen saturation (SaO 2 ) & arterial oxygen tension (PaO 2 )
* low arterial oxygen level generally suggests PCP or severe involvement
by other pathology
Blood tests
* relative leucocytosis suggests bacterial infection
* serology for atypical pneumonia
CT scan of chest
* helps to delineate the extent of parenchymal, lymph node and pleural
involvement
* identifies KS lesions even when chest X-ray is normal
* investigation of choice for suspected bronchiectasis
Fibreoptic bronchoscopy - microbiological and histocytological
examination
* bronchoalveolar lavage (BAL) is quite sensitive for diagnosing PCP (if
no yield on sputum examination)
* transbronchial biopsy is more sensitive than BAL and may be needed for
diagnosing mycobacterial and fungal infections and interstitial
pneumonitis
Open lung biopsy
* last resort for unexplained severe pulmonary symptoms that are thought
to be related to lung pathology

36
 Presentation Diagnostic approach

Diarrhoea and Stool examination

fever * examination for pus cells, ova and cysts, culture for usual enteric
pathogens, Cryptosporidium, Microsporidium, assay for Clostridium
difficile t o x i n (if history of antibiotics use) , direct smear and culture for
mycobacteria, fresh stool for Giardia; culture for sexually transmitted
agents (for proctitis); will require multiple specimens examination
Gastroduodenoscopy and colonoscopy
* may be needed if negative stool studies and failure to respond to
symptomatic treatment and empirical anti-bacterial treatment
* duodenal biopsy for CMV, mycobacteria, Cryptosporidium,
microsporidium (generally needs electron microscopy)
* colonic biopsy for CMV, mycobacteria, Cryptosporidium, herpes simplex
virus
Blood culture
* for mycobacteria if suspect tuberculosis or MAI
* enteric pathogens, particularly Salmonella, can lead to septicaemia

Fever, headache, CT scan brain

± focal * useful for detecting mass lesions e.g. cerebral toxoplasmosis, lymphoma,
neurological tuberculoma
deficits * aids differentiating various causes from sites of involvement and
appearances
* determines necessity and feasibility of performing lumbar puncture
Lumbar puncture
* diagnostic procedure for meningitis
* may support the diagnosis of CMV encephalitis
Blood tests
* serology for toxoplasma, CMV and syphilis
* cryptococcal antigen, complete blood count
* blood culture for e.g cryptococcus, Mycobacterium tuberculosis
MRI scan of brain
* more sensitive than CT scan, used when CT is negative but suspect
focal brain lesion especially progressive multifocal
leucoencephalopathy (PML)
Brain biopsy
* may be indicated when mass lesions fail to respond to anti-
toxoplasmosis therapy, may definitively diagnose PML, lymphoma,
toxoplasmosis or other diseases

37
 Presentation Diagnostic approach

Persistent fever Chest X-ray

of unknown * may reveal infection or neoplasm without yet manifestation of overt
origin (PUO) respiratory symptoms
Cultures
* blood culture ( to include mycobacteria and systemic fungal infection),
sputum and urine cultures
Blood tests
* complete blood count, liver and renal function tests, lactate
dehydrogenase level, serum cryptococcal antigen
CT scan abdomen
* when suspecting lymphoma or focal lesions of liver or spleen
Bone marrow biopsy
* for diagnosing MAI, Mycobacterium tuberculosis or lymphoma, especially
when there is cell count abnormalities
Lumbar puncture with CSF studies
* may be indicated when clinical evaluation and other investigations are
negative, even though there are no symptoms referrable to the central
nervous system
Others
* exclude drug reaction
* empirical therapy for secondary infections, symptomatic treatment or
antiviral therapy if symptoms are attributed to HIV

38
 3.3 Laboratory assessment of HIV-infected patients

Besides clinical assessment, laboratory investigations are essential in the overall

evaluation and staging of patients with HIV infection. They include basic haematological
and biochemical tests, immunological, serological and virological tests. Baseline followed by
serial tests are necessary as the trend of results yields much more useful information and is a
better guide to clinical management.

CD4 lymphocyte count

39
 CD4 lymphocyte (T-helper or T4 cell)
CD4 count & HIV-related count is unquestionably the single most
complications# important laboratory marker in the
management of HIV-infected individuals. A

CD4 >500/ul falling trend reflects immunosuppression,

* Guillain-Barre syndrome the degree of which is dependent on the
* Idiopathic thrombocytopaenia extent of immune destruction caused by
HIV. Some people advocate the use of CD4

CD4 200-500/ul percentage which is less affected by

* Constitutional diseases individual fluctuation and variation in
* Dermatophytosis number of absolute lymphocytes.
* Seborrhoeic dermatitis
* Molluscum contagiosum A low (<200/ul) or declining CD4 le v e l
* Tuberculosis is usually in parallel with the clinical
* Bacterial infections deterioration and is a useful prognostic
* Herpes simplex infection indicator for progression to AIDS. It should
* Oral candidiasis be noted, however, that CD4 level has
* Herpes zoster diurnal variation and the count also goes
* Oral hairy leucoplakia down with acute infections. It is well
* Kaposi's sarcoma recognised that the development of
* Non-Hodgkin's lymphoma opportunistic complications correlate with
the CD4 level. Knowledge of one's CD4

CD4 50-200/ul count is helpful in suggesting the most

* Pneumocystis carinii p n e u m o n i a likely pathogens or disease processes for
* Cryptococcosis certain clinical presentations and thus guide
* Toxoplasmosis the appropriate investigations. In addition, a
* AIDS dementia complex CD4 count of less than 50/ul is found to be
associated with a poorer survival.

CD4 <50/ul
* Cryptosporidiosis
* Cytomegalovirus disease
* Mycobacterium avium complex
* Primary CNS lymphoma

#approximate reference CD4 level

only, may occur at higher or lower
level

CD4 count is used as a surrogate

marker for HIV disease progression in both
clinical management and trials. For instance,
Uses of CD4 count
it is used for deciding when to initiate PCP
* prognostic marker for disease
prophylaxis and sometimes antiretroviral
progression
therapy. However, the association of HIV
* correlates with complications
load with CD4 count has been shown to be
that are likely to occur at certain
variable. Some patients with a very low CD4
stage of HIV disease

40
* guides medical management level may fare well for a prolonged duration.
* surrogate marker for clinical Although a useful and widely employed
end-points of HIV infection marker, its interpretation should often be
treated with caution. Unfortunately direct
viral quantitation by, for example,
polymerase chain reaction, is currently only
a research tool. Nevertheless, CD4 count is
probably one of the best laboratory
indicators for immunological assessment as
well as for monitoring the efficacy of
antiretroviral therapy. In Hong Kong, CD4
enumeration by flow cytometry is available
at the Pathology Institute of the Sai Ying
Pun Polyclinic operated by the Department
of Health. As a general recommendation, the
CD4 level of HIV positive patients is
checked every 3 months unless the count is
rapidly falling and thus requires closer
monitoring.

Other virological, immunological, serological and blood tests

Apart from a low CD4 count, other

laboratory markers indicating poor
Laboratory prognostic markers prognosis include: low CD4:CD8 ratio, p24
* low/falling CD4 lymphocyte antigenaemia, low p24 antibody, raised
* reversed CD4:CD8 ratio s e r u m β2- m i c r o g l o b u l i n , r a i s e d s e r u m a n d
* raised β2- m i c r o g l o b u l i n a e m i a urinary neopterin level and diminished
* raised serum and urine neopterin cutaneous reaction to allergens. Generally,
* raised HIV p24 antigenaemia the CD4 to CD8 ratio is reversed and falls as
* reduced HIV antibodies HIV disease progresses. The reappearance
* reduced cutaneous cell-mediated of p24 antigen in the blood is associated
reaction with an increased viral burden and thus
poorer prognosis. However, p24
antigenaemia is not a sensitive surrogate
marker as many patients with advanced
disease do not have detectable antigen in

41
 the blood. A low or loss of antibody to p24
core antibody may be secondary to
increased production of. HIV antigen and
development of immune complexes.

β2- m i c r o g l o b u l i n i s a s u b u n i t o f t h e c l a s s I m a j o r h i s t o c o m p a t i b i l i t y c o m p l e x w h i l e
neopterin is a product of stimulated macrophages. Their serum level are raised as a result of
i m m u n e a c t i v a t i o n . A l t h o u g h h i g h l e v e l s o f β2- m i c r o g l o b u l i n a n d n e o p t e r i n a r e a s s o c i a t e d

with a poor prognosis, they are in general non-specific markers. Supplementing the
information (CD4, CD8 and their ratio) from T-cell subset tests, these virological and immune
markers may be measured every 6 to 12 months, depending on needs and resources
available. Skin tests for cell-mediated immunity (CMI) may provide additional clues to the
immunological status of the patient.

Serological tests are often used in the diagnostic workup for several opportunistic
infections. These include antibodies to CMV, toxoplasma and HSV (herpes simplex virus),
and cryptococcal antigen. Baseline documentation is useful and these tests are later
repeated when necessary. Also, infections sharing the same risk factors as HIV, such as
hepatitis B and C and syphilis can be surveilled regularly by serology.

Other blood tests useful in the management of HIV infection are: complete blood
counts with differentials, and liver function tests. For patients on antiviral therapy, a closer
laboratory monitoring for adverse effects is needed. For example, blood counts, creatine
kinase and liver function may be checked every month for zidovudine-treated patients
whereas amylase and urate level are also measured for patients on ddI or ddC.

Besides all these monitoring and surveillance tests, it is essential that patients at
their first consultation should have HIV antibody test repeated to ensure that the result is
correct.

42
 4. ORGAN/SYSTEM INVOLVEMENT &
SPECIAL CLINICAL ISSUES OF HIV INFECTION

4.1 Oral, gastrointestinal & hepatic manifestations

Oral problems

The oral cavity is commonly affected

Common oral lesions by infections or other complications of HIV

Candidiasis infection, usually relatively early in the

Hairy leucoplakia course of the disease. Oral candidiasis (OC)

Herpes simplex virus (HSV) often appears as whitish plaques (thrush)

Bacterial infections over buccal, pharyngeal mucosa or tongue.

gingivitis Diagnosis is usually clinical but may be

periodontal disease confirmed by potassium hydroxide stain or

ulcerations culture. It should be noted that thrush

abscesses represents only one form of candidiasis - the

Apthous ulcerations pseudomembranous form. It may also

Kaposi's sarcoma (KS) present in the erythematous form, as

epithelial hyperplasia (leukoplakia) or
produce angular cheilitis.

Oral hairy leucoplakia, which is virtually pathognomonic of the underlying HIV

infection, consists of white warty vertical folds along lateral and inferior aspect of the
tongue. Aetiologically it is related to Epstein-Barr virus (EBV). Though it usually causes
no symptoms, the unsightiness may warrant acyclovir treatment. Herpes simplex virus
(HSV) commonly presents as painful, rapidly ulcerating vesicles over palate, gingiva,
tongue or lip. Other conditions e.g. apthous ulcers, bacterial infections presenting as
gingivitis, periodontitis, stomatitis and abscesses may also occur. Maintenance of good
oral hygiene, topical antiseptics, appropriate antibiotics and surgical debridement/drainage
when necessary are important for the treatment of bacterial infections.

Kaposi's sarcoma (KS) may involve the palate, gingiva or tongue, and appears as
purple macule, papule or even fungating mass. Biopsy could establish the diagnosis if
there is uncertainty.

43
Retrosternal discomfort, dysphagia & odynophagia

These symptoms are usually caused

by oesophageal candidiasis,
Candidiasis cytomegalovirus (CMV) oesophagitis or
Cytomegalovirus (CMV) HSV oesophagitis. Candidiasis is the
Herpes simplex virus commonest cause of oesophageal infection,
Idiopathic ulcer often accompanied by oral candidiasis. In
the presence of OC and oesophageal
symptoms, it is rational to treat
presumptively for oesophageal candidiasis.
If there is poor response, one should
proceed with an endoscopy to exclude other
or concurrent pathology. Herpes virus
infection can cause very severe retrosternal
pain and the diagnosis is confirmed by
culture of ulcer tissue.

CMV often leads to large and solitary oesophageal ulcer. Histology may show the
characteristic large (cytomegalic) cells containing intranuclear or cytoplasmic inclusions.
T h e i n t r a n u c l e a r i n c l u s i o n m a y b e s u r r o u n d e d b y a s p a c e , g i v i n g t h e a p p e a r a n c e o f a n o wl's
eye” halo. Immunoperoxidase stain for early antigen may also assist in the diagnosis.
Idiopathic oesophageal ulceration usually occurs in those patients who have already
developed AIDS. It mainly situates in the mid to distal oesophagus and is single and less
than 1 cm in about 40% of the cases. It may respond dramatically to steroid. In resistant
cases, thalidomide may be useful. Other causes such as reflux oesophagitis, which may be
exacerbated by non-steroidal anti-inflammatory drugs (NSAIDs) or even zidovudine, can
also be the cause of oesophageal symptoms.

44
Diarrhoea - gastrointestinal infections & other diseases

Diarrhoea is a very common complaint

in patients with HIV, regardless of the stage
of the disease. Enteric pathogens are usually
the cause but the causative microorganism
Causes of diarrhoea may not be easily isolated, leaving the
clinicians to attribute the symptom to HIV
Bacteria infection itself. Acute infective diarrhoea is
Salmonella species commonly due to Salmonella, Shigella or

Shigella flexneri Campylobacter enterocolitis, which can

Campylobacter jejuni result in septicaemia or may run recurrent

Clostridium difficile courses. Severe abdominal pain can occur,

Protozoa or blood and mucus may be passed in the

Cryptosporidium stool. Stool examination usually reveals pus

Microsporidium cells, and culture is important to confirm the

Isospora belli diagnosis. Similar response to appropriate

Giardia lamblia antibiotic is seen as in immunocompetent

Entamoeba histolytica subjects but the course of treatment may

Viruses need to be longer. Clostridium difficile m u s t be
Cytomegalovirus excluded if there is history of antibiotic
Herpes simplex virus therapy prior to onset of the diarrhoea.
Human immunodeficiency
virus Chronic diarrhoea is defined as
Mycobacteria motions ≥ 2/day, lasting for more than 1

Mycobacterium avium- month. It can cause malabsorption, marked

intracellulare weight loss and significant debility with

Tumour p o o r q u a l i t y o f l i f e i n s e v e r e c a s e s . “ S lim
Kaposi's sarcoma d i s e a s e” , c o m m o n l y f o u n d i n A f r i c a n A I D S
patients, is a good demonstration of its
impact. Classical pathogens in HIV setting
include Cryptosporidium, Isospora belli,
Microsporidia, a n d Mycobacterium avium-
intracellulare ( M A I ) .

Cryptosporidiosis is usually self-limiting in immunocompetent people. In HIV-infected

patients, however, it can cause persistent and profuse watery diarrhoea, especially in cases
of advanced immunodeficiency. Cryptosporidiosis can result in dehydration and marked
wasting. Low-grade fever is common and abdominal cramp can be severe. Diagnosis can be
made from multiple stool examinations with modified acid-fast stain. Symptomatic and
supportive treatment with antidiarrhoeal agents, fluid and electrolyte replacements are
necessary. Antibiotics like paromomycin may be beneficial in severe cases unresponsive to
symptomatic therapy. Infection by Isospora belli resembles cryptosporidiosis clinically.
Diagnosis is established by the detection of large, oval oocysts in stool.
Microsporidia has lately emerged as another important enteric pathogen in patients
with AIDS. Typically a patient with microsporidiosis has no fever and the diarrhoea comes

45
and goes. Previously the diagnosis was usually made by electronic microscopy of duodenal
or jejunal biopsy tissue. Microsporidia (but not the species) can now be identified by light
microscopy examination of the stool with special technique.

The role of MAI in causing diarrhoea is not clear, though a causative or

contributory role seems likely in some cases. Stool or tissue examination can identify MAI.
Mycobacterium tuberculosis infection of the gut is uncommon. Clinical features and response
to treatment of Giardiasis are similar to immunocompetent patients. Entamoeba histolytica
rarely causes invasive colitis in HIV patients.

Cytomegalovirus can affect any site of the gastrointestinal tract. The commonest
manifestation of enteric CMV disease is colitis. It is characterised by diarrhoea, fever, lower
abdominal pain, and possibly haemorrhage. The presentation can mimic acute abdomen.
Complications like toxic dilatation, haemorrhage and perforation have been reported. The
diagnosis is usually made by upper and/or lower gastrointestinal endoscopic examination
with biopsy. AIDS-associated enteropathy is postulated as the cause for patients who
exhibit villous atrophy and malabsorption in the absence of identifiable pathogens. The
exact mechanisms of this entity remain controversial. In clinical practice, chronic diarrhoea
has to be distinguished from ano-rectal discharge from infections by sexually transmitted
agents like Neisseria gonorrhoea, herpes simplex virus and Chlamydia trachomatis , commonly
c a l l e d t h e “ Ga y b o w e l s y n d r o m e ” .

The principles of therapeutic interventions for enteric infections in HIV-infected

patients are (1) supportive therapy with fluids, electrolyte and antimotility drugs; (2) specific
therapy, if available; (3) chronic suppressive therapy if there is symptomatic improvement
with the drugs and yet recur badly after stopping the treatment and (4) octreotide (a
somatostatin analogue) which has been reported to be effective in refractory diarrhoea.
Very rarely, non-infective causes e.g. Kaposi's sarcoma may cause symptomatic diarrhoea
and necessitate chemotherapy.

Hepatobiliary diseases

Involvement of the hepatobiliary tract

Parenchymal diseases may occasionally occur in the course of HIV
Cytomegalovirus infection. Manifestation varies from

Cryptosporidium asymptomatic elevation of the liver enzymes

Lymphoma to frank cholecystitis or cholangitis with
Kaposi's sarcoma recurrent, severe pain or acute illness that
Hepatitis viruses B,C,A may require surgical intervention.
Drug induced

Cholecystitis/Cholangiopathy
Cytomegalovirus

Cryptosporidium
Kaposi's sarcoma

46
 Parenchymal liver disease can be caused by a variety of infections or neoplasia.
Cytomegalovirus or mycobacteria (MAI or MTB) can cause biochemical abnormality with or
without pain, fever or hepatomegaly. Lymphoma and Kaposi's sarcoma can both infiltrate
the liver. Hepatitis viruses, especially B, C, and to a lesser extent A, are agents to consider in
frank hepatitis as they share similar risk factors as HIV and are thus more prevalent in this
group of patients. The host's immune response plays an important role in the pathogenesis
of liver damage in viral (especially hepatitis B virus) hepatitis. Such damage, and thus
symptomatology, may be more severe when the patient is still immunologically competent.
Drug-induced liver damage has also to be excluded as several drugs commonly used in the
setting of HIV infection can cause deranged liver functions, e.g. zidovudine, ketoconazole
and rifabutin. Serological testing, ultrasonic examination of the hepatobiliary system and
liver biopsy are useful investigations. Both histology with usual and special stains, as well
as culture, are necessary in tissue examination.

A c a l c u l o u s c h o l e c y s t i t i s a n d A I D S c h o l a n g i o p a t h y a r e u s u a l l y a e t i o l o g i c a ll y l i n k e d t o
CMV or Cryptosporidium infection, though rarely they can be due to Kaposi's sarcoma.
Recurrent right upper quadrant pain, fever or jaundice can be the presenting symptom.
Ultrasonogram may reveal a thickened-wall gall-bladder with narrowed lumen, without
stones and sometimes with dilated intrahepatic ducts. Endoscopic retrograde cholangio-
pancreatography (ERCP) can both be diagnostic and therapeutic. It shows extrahepatic duct
dilatation in case of cholangiopathy, with a picture similar to sclerosing cholangitis.
Symptomatic relief may be obtained with sphincterotomy if there is no response to specific
therapy for CMV or Cryptosporidium. Systemic chemotherapy may be considered if the
pathology is due to Kaposi's sarcoma. Cholecystectomy may be necessary when other
measures failed.

47
 4.2 Respiratory manifestations

Respiratory disorders, both upper respiratory and pulmonary, are common

complications in HIV infection. They range from increased frequency or severity of
infections due to common pathogens like influenza, bronchitis, bacterial pneumonia or
tuberculosis to occurrence of opportunistic infections e.g. Pneumocystis carinii and
cryptococcal pneumonia, which can be life-threatening in severe cases. Two pathologies
can occasionally occur together, e.g. superimposed opportunistic infection in pulmonary
Kaposi's sarcoma, or concurrent CMV infection in Pneumocystis carinii pneumonia (PCP).
Anti-pneumocystis treatment and prophylaxis is one of the most important breakthrough in
the management of HIV infection, which have reduced considerably morbidity and mortality
associated with PCP. Antiretroviral therapy with zidovudine may also have a contributory
role in improving the patients ’ quality of life.

Pneumocystis carinii pneumonia

PCP is the primary AIDS-defining

Procedure for sputum induction
* fast ≥ 4 hours before induction
* thoroughly clean mouth by
brushing & gargling
* use 3% hypertonic saline &
ultrasonic nebuliser
* instruct patient to inhale &
exhale with mouth through the
mouthpiece
* expectorate coughed-up sputum
(not saliva) into the container
illness in over half of the AIDS patients in
many series, and the life-time risk was once
estimated to be nearly 80%. In Hong Kong,
it has remained the commonest AIDS event
over the past decade. The chance of getting
PCP is much higher when one’s CD4 count
falls below 200/ul, and the diagnosis must be
considered in all patients presenting with
pneumonia. The taxonomic position of P.
carinii remains unclear as a protozoan or
fungus though recent research was more in
favour of the latter.

Clinically, patients experience insidious

(2 weeks or more) development of fever, dry
Diagnosis of PCP
cough, night sweats, weight loss and
progressive shortness of breath. Chest is
Presumptive
usually clear on examination. X-ray of the
clinical features
chest classically shows bilateral perihilar to
CXR
diffuse alveolar or interstitial infiltrates (Fig
hypoxaemia
5). Spontaneous pneumothorax or apical
response to high dose
disease can occur, especially in those
co-trimoxazole
receiving aerosolised pentamidine as
prophylaxis. Pleural effusion or normal X-ray
Definitive
are uncommon. Hypoxaemia is usually
induced sputum
evident, as shown by a lowered SaO2 or
bronchoalveolar lavage
transbronchial biopsy P a O 2, a s i s a r a i s e d l a c t a t e d e h y d r o g e n a s e

level.

48
 A high index of suspicion is essential
for diagnosing PCP as this could well be the
first presentation of previously unknown
HIV positive patients. Definitive diagnosis
can usually be established with
microbiological examination whereas
histological evidence is necessary in
difficult cases. Induced sputum with
hypertonic saline for P. carinii i s a relatively
simple and efficient method of arriving at the
diagnosis, with a sensitivity of >90%
reported in some studies. However, the
potential risk of arterial desaturation has to
be borne in mind. Giemsa or silver stain are
used for detection of the trophozoite or cyst.
Monoclonal antibody examination can
improve the yield. In case of sputum
negativity, one may proceed to
bronchoscopic examination with
bronchoalveolar lavage (BAL), which has a
diagnostic yield of over 95% for PCP.
Transbronchial biopsy may be indicated if
BAL is negative or when other pathogens
e.g. cytomegalovirus or mycobacteria are
also suspected.

Not uncommonly, prompt treatment has to be started for a presumptive diagnosis of

PCP, based on compatible evidence clinically and investigationally. The preferred treatment
of PCP is high dose trimethoprim-sulphamethoxazole (co-trimoxazole) for three weeks.
Intravenous administration is necessary in moderate and severe cases, at least in the initial
period. Unfortunately, it has been shown that adverse reactions occurred in about half of all
patients taking co-trimoxazole - usually presenting as nausea, vomiting, allergic rash, fever
and cytopaenia. These may lead to the discontinuation of therapy in up to 20% of all cases.
W h e n t h e P a O 2 is less than 70mmHg, addition of corticosteroid within 72 hours of starting

anti-pneumocystis therapy can significantly reduce the risk of death by half. Intravenous
pentamidine has to be used in case of intolerance to co-trimoxazole. With pentamidine, side
effects like renal impairment, pancreatitis, hypotension, hypoglycaemia followed by
hyperglycaemia and also electrolyte disturbances may occur. Other alternative drugs for
mild to moderate PCP include dapsone and trimethoprim, clindamycin and primaquine, and
atovaquone. Trimetrexate has been used as a salvage therapy for severe cases intolerant of
or unresponsive to both parenteral co-trimoxazole and pentamidine.

Preventive therapy, either primary (indicated when CD4 count is less than 200/ul or
patient has developed AIDS) or secondary (after an episode of PCP) , has been shown to be
very effective in reducing future occurrence of PCP. Again, co-trimoxazole is the first-line
drug if the patient can tolerate it. It has the additional advantage of protecting against
toxoplasmosis. In Hong Kong, the drug has been used in the public service for PCP
prophylaxis since 1989. The choice of second-line drugs for prophylaxis differs from places

49
to places. The options are aerosolised or intravenous pentamidine, oral dapsone with or
without pyrimethamine, and pyrimethamine-sulfadoxine (Fansidar).

Tuberculosis

HIV infection has re versed the declining trend of tuberculosis (TB) in developed
countries like USA. Tragically, it has also worsened the already severe problem of TB in
developing countries, especially Africa. Tuberculosis has once again become a major public
health issue globally as a result of the AIDS epidemic. In Hong Kong, roughly 10% of the
AIDS patients had disseminated tuberculosis as their initial AIDS-defining disease.
Mycobacterium tuberculosis ( M T B ) is a virulent pathogen and it causes disease relatively early
in the course of HIV infection, when the median CD4 count is about 350/ul. In places where
tuberculosis is endemic, development of TB in HIV positive patients is often via
reactivation of latent infection. Compared with non HIV-infected subjects, the frequency and
the progression rate of clinical tuberculous disease is much higher in HIV-infected people.

The clinical presentation of TB in HIV-

infected patients is similar to that of the
TB in the setting of HIV g e n e r a l p o p u l a t i o n w h e n t h e h o s t’ s i m m u n e
* features dependent on degree system is still relatively intact. Atypical
of immunosuppression manifestation is, however, not uncommon
* can have non-specific symptoms when there is more advanced
* tendency of dissemination immunosuppression. Patients can present
* can atypical CXR with non-specific symptoms of fever,
* potentially treatable malaise, and weight loss without cough.
* multidrug-resistant TB More extra-pulmonary involvement,
worrisome disseminated infection, and more fulminant
and rapid progression may actually be the
clue to an underlying HIV disease in
tuberculous patients. Atypical chest X-ray
findings have been described e.g. lower
zone or diffuse infiltration, adenopathy and
rarely cavitation, particularly in those
patients with impaired cellular immunity. The
role of tuberculin test in the diagnosis of TB
can be controversial in places with endemic
TB or where mass BCG vaccination is
practised like that in Hong Kong. The
prevalence of positive sputum smear and
culture appears to be similar to HIV negative
patients. Lymph nodes, bone marrow, liver
and blood stream are potential sites to
recover MTB for making a definitive
diagnosis in case of disseminated disease.

50
 The BACTEC radiometric culture
system is a new, rapid and sensitive method
Treatment of tuberculosis for diagnosing mycobacterial disease. The
* good response to treatment growth and identification of species are
* combination chemotherapy with usually achieved within 2 to 3 weeks, being
4 drugs (isoniazid, rifampicin, faster for MAI than MTB. This enhances
pyrazinamide and ethambutol) the speed and efficiency of diagnosis and
for 2 months, followed by the application of control measures for
isoniazid & rifampicin tuberculosis. The rising prevalence of
* total duration of 9 months or more multidrug-resistant tuberculosis (MDR-TB)
* regimen for MDR-TB depends on with several major outbreaks in USA among
prevailing susceptibility or HIV-infected people have resulted in rapidly
determined sensitivity fatal disease in some cases. MDR-TB will
continue to be a big worry both
epidemiologically and management wise in
the future.

The response of HIV positive TB patients to treatment has been shown to be as good
as non HIV-infected ones. Early diagnosis and prompt treatment are essential both for the
health of the patient as well as for preventing the spread of tuberculosis in the public health
control programme for the disease. Longer duration of the standard anti-TB therapy is
recommended: a mininum of 9 months in total after initial 2 months with at least four drugs.
For disseminated disease or resistant strains, treatment has to be continued for one year or
more. Rifampicin, isoniazid, pyrazinamide and ethambutol are commonly used. Streptomycin
is less commonly used because of the need to be given through injection. Good drug
compliance is prudent. Isoniazid prophylaxis for selected candidates has been shown to
decrease the incidence of disease in some overseas studies. Treatment of MDR-TB can be a
problem; the regimen should consist of at least two drugs that the strain is sensitive to.

Mycobacterium avium intracellulare

Apart from TB, patients with HIV may also be affected by atypical mycobacterial
infection, which often occurs in advanced stage of HIV disease, with preceding AIDS
diagnosis. The commonest atypical mycobacterium is Mycobacterium avium intracellulare
(MAI), also called Mycobacterium avium complex (MAC). MAI is ubiquitous in the
environment, commonly found in soil, water and foodstuff.

51
 The respiratory and gastrointestinal
tracts are possible portals of entry for MAI.
Localised disease can occur but
Disseminated MAI disseminated MAI infection is much more
fever significant which characteristically occurs
malaise with a CD4 count of less than 100/ul.
night sweats Disseminated disease may present as fever,
weight loss weight loss, night sweats, diarrhoea,
diarrhoea abdodminal pain, hepatomegaly, anaemia or
abdominal pain an elevated serum level of alkaline
lymphadenopathy phosphatase. Chest X-ray may show
hepatosplenomegaly nodular, diffuse, or patchy infiltrates, with or
anaemia without hilar or mediastinal
pancytopaenia lymphadenopathy. MAI is recoverable by
raised alkaline phosphatase blood culture in more than 80% of patients
with disseminated infection. However, MAI
bacteraemia can be intermittent, especially
with a lighter load of organism. Repeated
culture may therefore be necessary before a
diagnosis can be made. The BACTEC
culture system has hastened the process of
obtaining positive culture, the result of
which is commonly available within 7 to 14
days. Bone marrow, liver, and lymph node
are other potential sites for isolation of MAI.
Sometimes the organism is only found in
sputum or faeces, the presence of which
may represent colonisation only. However,
the chance of subsequent dissemination in
such circumstances can be high.

Besides causing morbidity, studies have suggested that disseminated MAI infection
also adversely affects survival. Treatment is indicated to alleviate symptoms, improve
quality of life and hopefully improve survival. Life-long therapy is needed to reduce the
bacterial burden in the body and to suppress bacteraemia. Combination antimycobacterial
agents is used, consisting of at least two and usually 3 to 4 drugs. Clarithromycin, a new
macrolide, is one potent drug against MAI and should preferably be used. Other drugs
employed may include rifabutin, rifampicin, ethambutol, clofazimine, ciprofloxacin and
amikacin. Potential drug interactions have to be watched out for as affected AIDS patients
are usually taking multiple drugs.

52
Bacterial, viral, fungal & parasitic infections

Bacterial infections of the respiratory tract are commoner in patients with HIV infection
than the general population, particularly in drug users. The phenomenon is caused by the
underlying impaired immunological function at the level of B cell, macrophage, and
neutrophil. Pneumonia and sinusitis (often chronic) are common presentations whereas
increased incidence of bronchiectasis and bronchitis have been reported. For community-
acquired pneumonia, the most important organisms identified are Streptococcus pneumoniae
and Haemophilus influenzae, followed by Staphylococcus aureus, Mycoplasma pneumoniae a n d
gram-negative bacteria (though often n o s o c o m i a l ) i n c l u d i n g Pseudomonas aeruginosa. Clinical
presentations may be similar to those of immunocompetent people. Unlike opportunistic
infections, they occur in relatively early stage of the HIV infection. Bacteraemic spread and
recurrence are, however, common, especially with pneumococcal infection. Moreover,
Pseudomonas aeruginosa i n f e c t i o n of the lung and other sites have been increasingly reported
as a serious and recurrent complication of AIDS. The antimicrobial therapy used for bacterial
infections are similar to those occurring in HIV negative patients.

Viral infe c t i o n o f t h e l u n g i s p r o b a b l y
Pulmonary infections in HIV uncommon. The pathogenic importance of
CMV pneumonitis in HIV infection is

Protozoa controversial. Presentation is usually with

Pneumocystis carinii* diffuse interstitial pulmonary infiltrate and

Toxoplasma gondii hypoxaemia. More definitive diagnosis can

Mycobacteria be made from transbronchial biopsy to show

Mycobacterium tuberculosis * the specific cytomegalic inclusion bodies in

Mycobacterium avium lung tissue. Treatment with ganciclovir may

intracellulare lead to a better clinical outcome. Other rarer

Bacteria herpes viruses infection include herpes

Streptococcus pneumoniae* simplex pneumonitis and a lymphocytic

Haemophilus influenzae interstitial pneumonitis seen in children

Staphylococcus aureus which is caused by Epstein-Barr virus.

Mycoplasma pneumoniae
Pseudomonas aeruginosa Cryptococcus neoformans lung infection

Viruses is almost always affected in the presence of

Cytomegalovirus meningitis. Clinical manifestations are
Herpes simplex virus usually non-specific. However, pleuritic pain
Epstein-Barr virus is common and can be associated with

Fungi pleural effusion. Serum cryptococcal antigen

Cryptococcus neoformans is usually present. Histoplasmosis occurs in

Histoplasma capsulatum people living in or have travelled to endemic

Aspergillus areas. It is usually a disseminated disease
Candida with chest X-ray showing diffuse
reticulonodular and less commonly alveolar
* commoner infections infiltrate. Diagnosis is established from
culture of blood,

53
 respiratory specimens, lymph node or bone
marrow. Other fungi such as Aspergillus and
Candida species are rarely implicated as
pulmonary pathogens. Amphotericin is the
gold standard of therapy for these infections
though several azole drugs are also useful
for certain specific fungal infections of the
lung. Toxoplasma gondii can cause
pneumonia, albeit uncommon. Fever and
dyspnoea are common features. Serological
test for anti-toxoplasma antibody is usually
positive. Similar to fungal pneumonia, the
organism can often be recovered from
bronchoalveolar lavage with or without lung
biopsy.

Neoplasia & inflammatory disorders

These are less common complications

Neoplasms of the respiratory system in comparison with
Kaposi's sarcoma infections. Of these, Kaposi's sarcoma is the
Non-Hodgkin's lymphoma commonest tumour affecting the lung.
Inflammatory diseases However, KS involvement in the absence of
Lymphoid interstitial pneumonia cutaneous lesions is unusual.
Non-specific interstitial pneumonia Endobronchial, parenchymal and pleural
lesions can all occur, as well as intrathoracic
lymphadenopathy. Symptoms include
dyspnoea, fever, non-productive cough,
wheezing and haemoptysis. Chest X-ray
frequently shows diffuse nodular or linear
interstitial densities. Pleural effusion, hilar
and mediastinal lymph node enlargement
can be present. Endobronchial lesions
detected at bronchoscopy provides the
clinical diagnosis though a definitive
diagnosis requires bronchial or
transbronchial biopsy. Prognosis is
generally poor even with aggressive
combination chemotherapy. Non-Hodgkin's
lymphoma (NHL) infrequently affects the
lung as part of the disseminated disease.
Symptoms are non-specific. Prognosis is
poor and treatment is associated with a high
incidence of complications, particularly
intercurrent infections.

54
 Chronic lymphoid interstitial pneumonitis was previously an AIDS-defining illness in
children with HIV infection. Its aetiology remains unclear and diagnosis is made by biopsy.
On the other hand, non-specific interstitial pneumonitis has been described in some patients
presenting with pulmonary symptoms without identifiable pathogens. In this case, chest X-
ray shows diffuse interstitial infiltrates and histology reveals mixed mononuclear infiltration.

Penicillium marneffei

Penicillium marneffei i n f e c t i o n has emerged to become an indicator disease for AIDS in

Southeast Asia. In Hong Kong, Penicilliosis is an important major opportunistic infection
among local HIV/AIDS patients. In 1995, this disease has been officially included in the
surveillance case definition for AIDS in Hong Kong. Since the diagnosis of the first case of
penicilliosis in HIV-infected people in 1989 in Hong Kong, close to 10% of local AIDS
patients have developed this complication at some stage of their HIV disease.

The pathogen is a dimorphic fungus that is only found in Southeast Asia including
southern China. Human beings and bamboo rats are the hosts. Both healthy and
immunocompromised subjects who reside in or have travelled to the afflicted areas can be
infected. In patients with HIV/AIDS, penicilliosis generally occur with profound
immunosuppression, as evidenced by the fact that all local infected patients had a CD4
count less than 100/ul.

The patients typically present with systemic symptoms of fever, weight loss and
anaemia. Other common findings include lymphadenopathy, hepatosplenomegaly,
pulmonary and gastrointestinal symptoms, as well as skin manifestations such as papular
molluscum contagiosum-like lesions. Diagnosis is usually made by a positive blood or bone
marrow culture. Occasionally, the fungus may also be recovered from skin biopsy as well as
culture of respiratory specimens. Prompt diagnosis is important as treatment with
amphotericin B can be life-saving in the acute phase. Lifelong maintenance therapy with
antifungals like itraconazole is necessary to suppress the infection after acute treatment.
Some authors have also used itraconazole as initial therapy.

55
 4.3 Neurological manifestations

The neurological system, both central and peripheral nervous systems, can be affected
by opportunistic infections, tumours, HIV itself and drugs. Alternatively, the pathology can
be classified according to the anatomical site of involvement, which ranges from
asyptomatic HIV infection of the brain, meningitis, focal brain disease, o n - f o c a l’ brain
disease, myelopathy, peripheral neuropathy, myopathy to retinitis. Clinical presentations of
different underlying neurological diseases can be remarkably non-specific and overlapping.
Yet, a correct diagnosis is crucial for initiating appropriate intervention, particularly when a
treatable cause is the culprit. Neurological complications are associated with significant
morbidity and mortality, especially when the implicating disease is life-threatening or that
can result in major functional disability.

Meningitis - cryptococcal & other causes

Meningitis occurring in HIV-infected

Cryptococcal meningitis in HIV persons could be due to causes like
* subtle symptoms of fever, headache cryptococcal, HIV, tuberculous, syphilitic
& malaise infections or lymphomatous infiltration.
* neck stiffness usually absent Cryptococcus neoformans is one of the
* atypical CSF changes with mild commonest causes of meningitis leading to
pleocytosis & normal biochemistry neurological complication in AIDS patients.
* positive smear and cryptococcal It usually presents with a subacute onset of
antigen useful for diagnosis fever, headache and malaise without
* treatment with amphotericin B &/or meningeal signs. Nausea, vomiting and
fluconazole sometimes altered mentation and personality
* lifelong suppressive therapy needed change may also occur. CT scan of the brain
is necessary to exclude space occupying
lesion due to other opportunistic infections.
Cryptococcoma of the brain is uncommon.

C. neoformans can often be identified by Indian ink stain of the cerebrospinal fluid
(CSF). Protein and glucose level of the CSF may be normal or mildly abnormal, and there is
often only a mild lymphocytic pleocytosis. Diagnosis is confirmed by culture while a
positive CSF or serum cryptococcal antigen is also supportive of the diagnosis. Chest X-ray
is necessary to look for pulmonary involvement. Disseminated cryptococcal disease can
present with skin lesions resembling molluscum contagiosum and in this case blood culture
may be positive. Poor prognostic factors of cryptococcal meningitis include positive
extraneural culture, high CSF cryptococcal antigen titers, low CSF leucocyte (<20 cells/mm3)
and most importantly, abnormal mental state at presentation. In selected mild cases,
treatment with fluconazole may be adequate. However, for severe or resistant meningitis,
amphotericin is the standard treatment, at least for the initial period. Life-long maintenance
therapy with an anti-fungal agent like fluconazole is required to prevent relapse.
Other causes of meningitis in HIV setting are much less common. Tuberculous
meningitis may occur with disseminated MTB infection. CSF cytology may reveal lymphoma

56
cells in case of lymphomatous meningitis. HIV per se can also cause an aseptic meningitis
which usually occurs during relatively early stage of the infection. Neurosyphilis is always a
possibility to consider in patients presenting with neurological symptoms. It is important to
check syphilis serology and ask for relevant history to assist in the diagnosis.

Focal brain diseases

Space-occupying lesions of the brain

cerebral toxoplasmosis* in HIV-infected patients can be due to
progressive multifocal infection, tumour or an underlying vascular
leucoencephalopathy* pathology. Lesions may be single or
cryptococcoma, other fungal abscesses multiple, and onset may be acute or
tuberculoma subacute. Symptoms and signs depend on
herpes simplex encephalitis the site involved and may include
cerebral lymphoma* dysphasia, hemiparesis, cerebellar ataxia,
cerebral infarction cranial nerve palsies and seizures. Systemic
and non-focal neurological symptoms may
* classical or common disease also be present. Toxoplasmosis, progressive
multifocal leucoencephalopathy (PML) and
primary cerebral lymphoma are important
causes of focal cerebral pathology in
patients with AIDS.

Infection of the central nervous system

by Toxoplasma gondii is common in AIDS
Cerebral toxoplasmosis patients. It is actually the most frequent
* fever, headache, confusion & fit opportunistic pathogen to cause
* reactivation with positive anti- encephalitis or focal cerebral lesions.
toxoplasma antibody Patients usually present with headache,
* multiple ring-enchancing lesions on confusion, fever and lethargy. Seizures
CT or MRI scan occur in about 30% of patients. Common
* empirical treatment with focal signs include hemiparesis, ataxia and
pyrimethamine plus sulphadiazine cranial nerve palsies while dominant
o r c l i n d a m y c in nonfocal abnormalities may include
abnormal mental status, confusion and
psychomotor retardation. Toxoplasma can
also cause pneumonia, cardiomyopathy and
retinochoroiditis.

Since the majority of toxoplasmic encephalitis is due to recrudescence of latent

infection, the anti-toxoplasma IgG antibody is usually positive. Multiple ring-enchancing
lesions over the basal ganglia, frontal and parietal regions with CT scan give the classical
appearance described for toxoplasmosis. Pressure effect of the abscesses is common.
Sometimes the more sensitive investigation like magnetic resonance imaging (MRI) is
required to show up the multiple lesions. Definitive diagnosis relies on brain biopsy which is
usually not warranted. It is common practice to treat presumptively when the clinical
features, serological and most importantly the radiographic findings support the diagnosis.

57
There is usually clinical and radiographic response within 2 to 3 weeks, a phenomenon
which virtually confirms the diagnosis. If not, other or concurrent pathology has to be
excluded and a brain biopsy may be indicated. Lifelong maintenance treatment with
pyrimethamine, sulphadiazine and folinic acid supplement is necessary. Co-trimoxazole for
PCP prophylaxis has been shown to protect against cerebral toxoplasmosis.

Primary CNS lymphoma is a rare

complication of HIV infection, often ocurring
in AIDS patients with history of major
Primary CNS lymphoma opportunistic infections or KS, and a low
* advanced HIV disease CD4 count. The cell type is B-cell and
* focal deficits, seizures, Epstein-Barr virus, a likely causative agent,
confusion, headache has been found to be universally present.
* poor prognosis Clinical presentations include focal
neurological deficits and non-focal features
such as confusion, memory loss and those
of raised intracranial pressure. CT or MRI
scan of the brain usually shows discrete
hypodense contrast-enhancing lesions with
pressure effects. Differentiation from
toxoplasmosis can be difficult, and brain
biopsy (either stereotactic or open) may be
necessary for arriving at a definitive
diagnosis. If treatment is considered
appropriate, radiation therapy with or
without intrathecal chemotherapy is usually
employed. The prognosis is poor and
median survival is about 2 months despite
treatment. Death results from intercurrent
infections or lymphoma itself.

PML is another rare disease. It results

Progressive multifocal from JC virus infection of the central
leucoencephalopathy (PML) nervous system. Hemiparesis is the most
* progressive multifocal cerebral common presenting symptom. Fever, altered
deficits without confusion, consciousness, headache and seizure are
fever and headache usually not part of the presentation and the
* white matter demyelination absence of these features can help in
shown up in MRI differentiating from focal neurological
* poor prognosis complications arising from other causes.
MRI scan is preferred to CT scan for PML.

58
 It usually reveals non-enhancing
asymmetrical white-matter lesions without
mass effect. Brain biopsy is required for a
definitive diagnosis. The disease runs
variable course but is often fatal. There is as
yet no treatment of proven value although
cytosine arabinoside has been shown to
have some therapeutic effects in a number of
anecdotal reports.

HIV-related neurological complications

HIV itself commonly affects the

nervous system, the presentation of which
ranges from a dementing illness (HIV
encephalopathy), myelopathy, to that of
peripheral neuropathy (including a
predominantly sensory neuropathy,
autonomic neuropathy and demyelinating
neuropathy). Myopathy has also been
described. Except for demyelinating
neuropathy (in acute or chronic form) and
aseptic meningitis, all disorders appear at a
stage of moderate to severe
immunosuppression.

H I V e n c e p h a l o p a t h y o r AIDS dementia
complex (ADC) usually occurs in
AIDS dementia complex (ADC) symptomatic HIV-infected patients. It is
* occurs in late HIV disease characterised by a subcortical dementia
* affects concentration, thinking, developing over weeks or months. During
balance, fine movement and the workup, it is important to rule out
social interaction opportunistic complications of the brain,
* exclude other causes of dementia psychiatric problems such as depression or
* may respond to high dose anxiety and chronic drug use e.g.
zidovudine benzodiazepine intoxication which can mimic
AIDS dementia complex. All three areas of
cognitive, motor and behavioural functions
may be affected, resulting in poor
concentration, mental slowing, tremor, poor
coordination, ataxia, and apathy. Early stage
may only reveal subtle physical signs like
impaired rapid alternate movements of
fingers and abnormal tandem gait. Cerebral
atrophy is evident on CT scan. CSF usually
shows mild mononuclear pleocytosis, raised

59
 protein and markers of immune activation - β

2 microglobulin and neopterin. However, no

investigations are diagnostic for ADC. They
are usually used to, instead, exclude
treatable infections and thus indirectly
support the diagnosis of ADC. About 50%
of the patients with ADC respond to high
dose AZT (1000mg daily), but it may take up
to 2 months or more for clinical effects to be
demonstrated.

A d i s t a l s e n s o r y a x o n a l neuropathy is
the commonest form of peripheral
neuropathy caused by HIV. Patients
Sensory peripheral neuropathy experience tingling or numbness sensation
* pins and needles in feet over the feet which may gradually spread
* motor disability uncommon proximally. Motor function is preserved
* symptomatic treatment with except that rarely walking is impaired by
amitriptyline, NSAIDs, narcotics severe feet pain. Treatment is symptomatic
and amitriptyline may be tried. Other
confounding causes of peripheral
neuropathy e.g. drugs like ddC has to be
excluded.

P a t i e n t s w i t h HIV myelopathy u s u a l l y p r e s e n t w i t h a s u b a c u t e f o r m o f p r o g r e s s i v e
spastic paraparesis without a definite sensory level. Decreased proprioception and vibration
are the commonest sensory abnormalities. Often ADC is also present. Exclusion of other
spinal cord pathology from infection or tumour is aided by MRI scan or myelogram with or
without simultaneous CT scan. Zidovudine may be tried but is usually of no therapeutic
value.

H I V - r e l a t e d myopathy r e m a i n s p o o r l y d e f i n e d i n t e r m s o f p a t h o g e n e s i s , t i m i n g o f t h e
disease and therapy. Steroid may ease the myopathy but pose the risk of worsening the
immunosuppression due to HIV. In HIV patients with features of myopathy, it is important to
consider zidovudine as the cause. This usually manifests as wasting of buttock muscles
with leg weakness. Improvement or resolution may result with early cessation of the drug.

60
Neurological diseases due to cytomegalovirus

Cytomegalovirus is a common
Polyradiculopathy pathogen in patients with AIDS, usually
Myelitis affecting gastrointestinal tract, nervous
Encephalitis system and eye but it can involve virtually
Chorioretinitis any organ of the body. CMV disease occurs
as a result of reactivation of latent virus due
to progressive impairment of cell-mediated
immunity. Neurological complications of
CMV take the form of polyradiculopathy,
myelitis, encephalitis, and most commonly
chorioretinitis.

CMV polyradiculopathy is
characterised by subacute onset of
ascending asymmetrical leg weakness,
CMV polyradiculopathy
numbness and pain, progressing to flaccid,
* ascending leg pain & paralysis
areflexic paraparesis or paraplegia. Sphincter
with areflexia
dysfunction, sacral paresthesia and low
* neutrophilia in CSF
back pain are common features since
* can have marked but delayed
myelitis may also be present. Patients often
response to ganciclovir
have severe immunosuppression and
* lifelong maintenance therapy
history of opportunistic infections. CSF
examination reveals polymorphonuclear
pleocytosis and moderately reduced glucose
level. Imaging studies may be necessary to
exclude compressive lesions of the spinal
cord. Prognosis is poor without treatment.
However, early therapy with ganciclovir
and/or foscarnet can give dramatic
response. Initial deterioration or delayed
improvement for weeks or even months may
occur with correct treatment. Anti-CMV
maintenance therapy has to be continued
indefinitely.

C M V encephalitis i s a s u b a c u t e p r o c e s s t h a t d e v e l o p s o v e r d a y s t o 1 o r 2 w e e k s . T h e
clinical presentation is progressive personality change, obtundation, headache, fever and
fits. CT brain scan is usually unremarkable. MRI scan may show non-specific periventricular
contrast enhancement due to tissue necrosis. Again polymorphonuclear pleocytosis may be
found in CSF. Treatment is with ganciclovir but the efficacy is unknown.

61
 CMV retinitis is a frequent
complication in AIDS patients with
CMV retinitis advanced immunosuppression. It is
* symptoms of floater, blurred increasing in incidence and importance. It is
vision, and visual field loss the commonest opportunistic infection in
* characteristic though non-specific patients who had already progressed to
retinal changes AIDS in Hong Kong. Sometimes it is the
* essentially a clinical diagnosis primary presenting AIDS-defining illness.
Retinitis usually begins unilaterally, but not
uncommonly it progresses to involve both
eyes because of CMV viraemia. Patients
present with floaters, blurring of vision or
less commonly, visual field loss.
Fundoscopic examination typically shows
Management of CMV retinitis
areas of retinal oedema, and perivascular
* induction treatment with IV
haemorrahge and exudate (classically
ganciclovir or foscarnet, depending
on tolerance and response
described as cottage cheese and catsup
appearance). Initially, these changes may be
* may use combination treatment
found in the periphery of the retina. If left
in case of poor response
untreated, the abnormalities progress to
* lifelong suppressive therapy
involve the macula and optic disc.

All patients with AIDS or CD4 count below 100/ul should be regularly monitored for
development of CMV retinitis, although the disease can also occur at earlier stage of HIV
infection. The diagnosis is made clinically and prompt treatment with antivirals like
ganciclovir is necessary. The major side effect of ganciclovir is bone marrow suppression,
which can substantially limit its tolerance, especially in patients receiving concomitant
zidovudine treatment. Products like G-CSF may be useful to counteract its most profound
toxicity of neutropaenia. Foscarnet has been shown to be at least as effective as ganciclovir
in treating CMV retinitis and apparently gives a survival benefit, possibly through its anti-
HIV effect. It has a different spectrum of side effects compared with ganciclovir, and is in
general less well tolerated than ganciclovir. Ganciclovir resistance has been described, and it
is possible that the same can happen with foscarnet.

In case of poor response to treatment with either agent, the alternate drug or a
combination of the two should probably be tried although there is yet no good study to
support this approach. Lifelong maintenance therapy is needed after 3 weeks of induction
treatment, to lower the chance of relapse. Insertion of long term venous access device has to
be considered as both drugs need to be administered intravenously. Clinical trials on the use
of oral ganciclovir is now in progress. Initial results showed that it is effective for
maintenance therapy, though an earlier relapse is expected compared with intravenous
ganciclovir. Expense is another disadvantage for this convenient alternative.

62
 4.4 Skin manifestations

Bacterial Fungal infections Viral Inflammatory Miscellaneous

infections dermatophytosis infections dis. Neoplastic
bacterial folliculitis pityriasis versicolor herpes zoster eosinophilic Kaposi's sarcoma (KS)
boil candidiasis herpes simplex folliculitis Arthropod
impetigo cryptococcosis molluscum seborrhoeic Scabies
skin abscess penicilliosis contagiosum dermatitis
s y p h i l i s ( 1 o & 2 o) wart psoriasis
tuberculosis drug eruption
atypical
mycobacterium
bacillary angiomatosis

Skin diseases, some relatively mild and

also found in HIV negative subjects, are
very common in HIV positive patients at
Features of skin diseases in HIV various stages of the infection. In some
* occur in unusual setting cases, skin findings may be the earliest sign
* increased severity and may alert one to the underlying HIV
* unusual clinical appearance disease. Early recognition of these
* recurrent course cutaneous manifestations can facilitate
* manifestation of systemic subsequent optimal management of HIV
opportunistic infections infection. The clinical courses of many skin
* abnormal response to diseases may, however, be altered in
conventional treatment different ways by concomitant HIV
infection, especially when immune
impairment gradually advances.

HIV infection should be suspected when a cutaneous disease occurs in an unusual

s e t t i n g e . g . m u l t i d e r m a t o m a l h e r p e s z o s t e r o c c u r r i n g i n a y o u n g h e a l t h y a d u l t . Herpes zoster
in immunocompromised patients tends to be more chronic and severe and tends to involve
more than one dermatome. Thoracic dermatomes are most vulnerable though any dermatome
can be affected. Deforming scars, severe post-herpetic neuralgia and recurrent disease are
p o t e n t i a l c o m p l i c a t i o n s o f t h i s f r e q u e n t i n f e c t i o n i n s u b j e c t s w i t h H I V . S i m i l a r l y , KS i n a
young individual is strongly indicative of HIV disease.

Minor skin conditions can be of increased severity if they occur together with HIV
i n f e c t i o n . O n e e x a m p l e i s seborrhoeic dermatitis w h i c h i s v e r y c o m m o n i n H I V - i n f e c t e d
people and is characterised by thick, scaly plaques with inflammation. Apart from commonly
affecting the nasolabial and glabellar regions, more extensive involvement of face and trunk

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m a y b e s e e n . Psoriasis i s a l s o i n c r e a s e d i n f r e q u e n c y a n d s e v e r i t y i n H I V p o s i t i v e p a t i e n t s ,
a s w e l l a s skin infections l i k e f o l l i c u l i t i s , f u r u n c l e , w a r t a n d s u p e r f i c i a l f u n g a l i n f e c t i o n s .

As a result of pronounced severity and extent of skin diseases in HIV infection,

u n u s u a l c l i n i c a l p r e s e n t a t i o n m a y o c c u r . Molluscum contagiosum i n f e c t i o n c a n b e v e r y
extensive and involve extragenital sites, particularly the face which is very unusual in non
H I V p o s i t i v e p a t i e n t s . Herpes simplex i n f e c t i o n m a y b e c o m e d i s s e m i n a t e d d u e t o p o o r h o s t
i m m u n i t y . Scabies m a y b e w i d e s p r e a d a n d m a n i f e s t a s a n e r y t h e m a t o u s p a p u l o s q u a m o u s
e r u p t i o n . Hypersensitivity reaction t o d r u g s i s m o r e f r e q u e n t a n d s e v e r e w i t h c o n c o m i t a n t
HIV infection. Drug eruption due to co-trimoxazole is a good example.

Skin lesions can also be part of a

systemic opportunistic infection .
Significance of HIV-related skin Disseminated cryptococcal infection can
diseases give rise to the typical skin-coloured
* alert one to the underlying HIV papules with central umbilication, which
infection resembles molluscum contagiosum.
* allow diagnosis of systemic Penicillium marneffei infection may present
infections with erythematous maculopapular rash.
* hamper quality of life Inflamed, tender nodules or ulcerating
* treatment important in overall lesions are skin manifestations of systemic
patient care mycobacterial infection. Skin biopsies for
histology and appropriate culture are
indicated when diagnosis is uncertain, or
when disseminated infections are suspected.
Bacillary angiomatosis, a vascular
proliferative process caused by Rochalimaea
henselae, presents most commonly with
multiple red skin papules/nodules. It may be
mistaken as KS. Differentiation by biopsy
and culture is prudent as it may cause
visceral disease and death if untreated.
However, treatment with erythromycin is
usually effective.

Response to conventional treatment of skin diseases is sometimes unsatisfactory in

HIV-infected individuals. Higher doses of medication, additional treatment, prolonged
therapy or supplementary surgical procedures may be needed. Superficial folliculitis,
eosinophilic folliculitis, seborrhoeic dermatitis and dermatophytosis are common examples.
Because of the tendency to relapse, therapy may have to be maintained indefinitely. In some
cases the quality of life may be hampered due to the accompanying disfigurement (e.g.
extensive cutaneous KS or severe symptoms e.g. intense pruritus due to eosinophilic
folliculitis). Although the skin problems are usually not life-threatening, management of
these conditions in HIV-infected patients should never be neglected.

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 4.5 Sexually transmitted diseases & HIV

Epidemiologically, sexual transmission

accounts for 70-80% of all HIV infections
Synergy of HIV & STDs worldwide. HIV is, by and large, a sexually
* STDs enhance HIV transmission transmitted agent, and the infection can
* HIV alters features of STDs coexist or found together with other sexually
e.g. more severe, atypical course, transmitted diseases (STDs) as they share
poor response to treatment similar routes of transmission. In addition, it
* ?STDs as cofactor for HIV has been shown that ulcerative (syphilis,
disease progression herpes and chancroid) or inflammatory
* presence of STDs prompts (gonorrhoea and chlamydial infection) STDs
HIV testing can increase the chance of contracting HIV,
presumably through facilitation of fluid
exchange during sexual contacts.

The incidence and prevalence of STDs in a population are valuable indices of the
underlying HIV problem or the potential risk for its spread. Surveillance of HIV infection
among people with high risk sexual behaviours can be achieved by offering HIV tests at
STD clinics.

In clinical practice, immunosuppression caused by HIV can worsen the clinical

course and response to therapy of other STDs. STDs in HIV positive people are also
important in that some agents, e.g. herpes simplex virus, have been implicated as possible
co-factor for hastening the progression of HIV disease. An integrative approach is desirable
in the prevention and control of STDs and HIV, both in public health context and in the
provision of patient care. Some of the more common or important STDs are discussed below.

Genital & anorectal herpes

Herpes simplex virus infection of the

genital organs, usually by type II, is
Herpes infection in HIV commonly seen in HIV infection. The
* may be severe & recurrent disease can be a primary infection or may
* distressing symptoms, may run recurrent courses. It appears as painful
hasten HIV disease progression papules over the affected sites, progressing
* an AIDS-defining condition if to vesicles and ulcers. Anorectal herpes can
ulcers persist for more than 1 result in proctocolitis and presents with
month rectal pain, discharge and associated
* acyclovir useful for treatment perianal skin lesions. Clinical suspicion of
and prophylaxis HSV infection can be confirmed by viral
culture and isolation of the organism.
Histological examination of perianal
ulceration may be needed if it is persistent.
HSV infection may be more severe in HIV positive individuals than normal subjects -
the lesions tend to be more invasive, slower to heal and associated with prolonged viral
shedding. Systemic features of fever, malaise and headache may be present in severe cases.

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For recurrent disease, patients may have prodromal symptoms of tingling and paraesthesia
when the herpes is relapsing, in which case early treatment may abort the attack.

In the management of active herpes, the pain may partially be alleviated by bathing the
lesions in warm saline. Adjuntive analgesic is usually necessary. Acyclovir, the specific
anti-herpes drug, is still largely effective in treating overt HSV infection in patients with HIV,
although some AIDS patients may fail to respond because of viral resistance. Foscarnet has
been shown to be effective in acyclovir-resistant infections. Similarly, acyclovir prophylaxis
is of value in preventing symptomatic relapse of herpes in HIV-infected patients.

Genital & anorectal wart

Genital wart (condyloma acuminatum) is caused by human papillomavirus. It presents

as multiple fleshy, nodular lesions at the anogenital regions. Often the lesions are painless
and asymptomatic. Diagnosis can be made clinically. Treatment of anogenital wart includes
topical podophyllin, liquid nitrogen therapy, electrocautery or surgical excision for large
lesions. Recurrences are, however, very common irrespective of the form of treatment.
Human papillomavirus has also been suggested to have a role in causing anal carcinoma in
patients with HIV.

Syphilis

Even though penicillin has made a

dramatic impact on the incidence of syphilis,
Syphilis in HIV this disease is still common in many parts of
* more aggressive clinical course the world. Among HIV-infected patients, the
* neurosyphilis more common diagnosis and management of syphilis can
* may have negative serology be difficult because of the
* treatment with procaine penicillin immunosuppression. The clinical
* monitor response after therapy manifestations, serological response,
occurrence of complications and response
to standard treatment of syphilis may all be
altered by concurrent HIV infection. Clinical
course may be prolonged and more
aggressive. There have been reports of
secondary syphilis confirmed by skin
biopsy while both non-treponemal and
treponemal tests were negative.

Incidence of neurosyphilis is increased in patients with HIV. There are various forms of
presentation - asymptomatic, meningovascular, parenchymatous or polyradiculopathic.
Serum and CSF syphilis serology is essential in investigating HIV-infected patients with
neurological symptoms although it can be unreliable in neurosyphilis occurring in HIV
positive patients. In a series of 42 patients, 21% had a negative VDRL reaction. Other CSF
abnormalities and clinical correlation are especially important in these cases. Because of the
high chance of treatment failure, procaine penicillin with or without probenicid or soluble

66
penicillin should be given for 2 to 3 weeks, depending on the stages. Benzathine penicillin
may also be used in early stages of syphilis. Monitoring of syphilis serology can be useful
to follow up response to treatment and future relapse.

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 4.6 Malignancy & HIV

Malignancy is the second major cause of complications in HIV-infected patients.

These opportunistic tumours have arisen because of the impaired or dysregulated immune
function from HIV infection. The majority of them are AIDS-defining illnesses and are
potentially lethal. Moreover, the quality of life of these patients can be severely affected.
Kaposi's sarcoma and non-Hodgkin's lymphoma (NHL) are classical examples of neoplastic
complications in patients with AIDS. Squamous cell carcinoma of the anogenital region and
cervix may also be associated with HIV infection.

Kaposi's sarcoma

KS was first described many years

ago as an indolent form of multicentric
KS in HIV vascular skin tumour found on legs of
* aggressive course with skin elderly men of Mediterranean origin. With
and/or visceral lesions the advent of immunosuppressive therapy,
* physical symptoms and another variant was noticed. Then came the
psychological stress aggressive type of AIDS-related KS
* individualised management secondary to HIV infection. An aggregation
of this unusual tumour, besides Pneumocystis
carinii p n e u m o n i a , in homosexual men in the
United States in early 1980s has actually
prompted investigation of the underlying
cause, which was subsequently identified to
be the human immunodeficiency virus.
Nowadays, the commonest form of KS
worldwide is that found in association with
HIV infection.

KS is the commonest tumour in HIV-infected patients. Histologically it is

c h a r a c t e r i s e d b y t h e p r e s e n c e o f p r o l i f e r a t i n g s p i n d l e - s h a p e d c e l l s . “ S a r c o m a ” o r “ t u m o u r”
are misnomers as KS is actually an angioproliferative disease with features of angiogenesis,
inflammation and oedema. It is not infrequently the first AIDS-defining disease among
homosexual or bisexual men with HIV, as it can occur relatively early in the course of HIV
infection. In Hong Kong about 8% of all reported AIDS cases presented initially with KS.
Research evidences suggest that a previously unidentified sexually transmissible agent is
the cause of AIDS-related KS.

Cutaneous involvement is almost universal in affected patients and is usually the

presenting feature. It typically appears as purple, violaceous or bluish-brown papule or
plaque. Face and trunk are most frequently inflicted and hundreds of lesions can occur in
severe cases. Blockage of the lymphatic drainage can lead to painful lymphoedema. Lesions
in the oral cavity are also common. Visceral involvement by KS, usually the gastrointestinal
tract and respiratory system, bears a poor prognosis. KS of the gut can cause pain,
obstruction, haemorrhage, or rarely diarrhoea. Diagnosis of KS is often made clinically from

68
its characteristic appearance. Sometimes biopsy is indicated for doubtful cases but false
negative result may occur due to its deep-seated location in the submucosa.

Treatment of KS in AIDS patients has to be individualised, depending on the extent of

the disease, symptoms, immunological status and presence of any concurrent complicatons.
When the disease is mild and limited to skin, observation and monitoring is preferred.
Intervention is, however, necessary for cosmetic reasons or to alleviate symptoms.
Intralesional chemotherapy with, say, vinblastine, may be considered. Alpha interferon is
found to be beneficial for patients with a good CD4 count, which may lead to prolonged
tumour regression. Radiotherapy is useful for isolated bulky lesions, bleeding tumour or
presence of tissue oedema. Involvement of internal organs or rapidly increasing skin lesions
are indications for systemic treatment. Single or combination chemotherapy are usually
employed. Vinblastine, vincristine, bleomycin and adriamycin are agents that are commonly
used. Zidovudine may serve as an adjunctive therapeutic agent. The frequency of
chemotherapy and drugs used have to be tailored according to the extent and presentation
o f t h e K S , a n d t h e p a t i e n t’ s r e s p o n s e t o a n d t o l e r a n c e o f t h e t h e r a p y . B o n e m a r r o w t o x i c i t y
of myelosuppressive drug and zidovudine is often a limiting factor for AIDS patients
although the neutropaenia may now be ameliorated by drugs like granulocyte colony-
stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF).

Malignant lymphoma

HIV infection is not infrequently

complicated by non-Hodgkin's lymphoma
NHL in HIV infection (NHL) . T h e s e a r e u s u a l l y h i g h g r a d e B - c e l l
* high grade B-cell type with chiefly lymphoma of immunoblastic or small
extranodal involvement noncleaved-cell type (Burkitt's), often
* may be Epstein-Barr virus related associated with Epstein-Barr viral genome in
* poor prognosis & response to the tumour. Unlike patients without HIV
combination chemotherapy infection, extranodal involvement (which
may be at unusual site like the brain, or
systemic disease) are common. When the
lymphoma affects the gastrointestinal
tract(commonly mouth, stomach and small
bowel), it appears as an ulcer or a mass.
Biopsy is necessary to establish the
diagnosis. Sometimes ‘ B’ symptoms of
fever, weight loss and sweating can be the
presenting feature. Sometimes, systemic
lymphoma may occur at a relatively early
stage of the HIV disease, in contrast to
primary CNS lymphoma which is invariably a
late complication. Staging of the lymphoma
by investigations is necessary, including
bone marrow examination and CT scan of
the abdomen.

For AIDS patients with low CD4 level and pre-existing opportunistic infections, they
usually tolerate conventional chemotherapy (e.g. CHOP or MBACOP) poorly and their
survival may be similar to or even worse than patients receiving less intensive therapy.

69
Patients in an early stage of HIV infection respond better to systemic chemotherapy and
may warrant a more aggressive approach. Prophylaxis with intrathecal methotrexate is often
indicated as progression to CNS involvement is common. The role of G-CSF in improving
management and survival in HIV-related NHL has yet to be established.

Hodgkin's disease h a s a l s o b e e n r e p o r t e d t o b e a s s o c i a t e d w i t h H I V i n f e c t i o n b u t i t s
incidence and importance have not been adequately assessed. They are treated with
regimen of MOPP (mechlorethamine, vincristine, procarbazine, prednisolone) or ABVD
(adriamycin, bleomycin, vinblastine, dacarbazine). The dose may have to be reduced
compared with standard recommendation.

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 4.7 Other HIV-related diseases

HIV and its related complications can affect virtually every organ of the body, giving
various clinical, biochemical, haematological and pathological manifestations. The majority
of the commoner or classical diseases has been dealt with in previous sections. The other
manifestations, which are usually rarer except for some haematological problems, are
discussed below.

Haematological problems

Cytopaenia of any of the three blood

cell lines can be caused by HIV,
Idiopathic thrombocytopaenic opportunistic infections, tumours, or drug
Purpura therapy. Idiopathic thrombocytopaenic
* autoimmune pathogenesis purpura ( I T P ) , d u e t o p e r i p h e r a l i m m u n e
* early HIV disease destruction of platelets, can occur in early
* usually mild to moderately low stage of HIV infection. The clinical picture
platelet count and asymptomatic can be similar to that occurring in HIV
* treat with zidovudine, platelet negative patients, with purpura, easy
transfusion, immunoglobulin bruising and rarely but potentially
and splenectomy as necessary catastrophic bleeding. Asymptomatic
thrombocytopaenia in patients with HIV
infection is not uncommon although
bleeding becomes more likely when the
p l a t e l e t c o u n t d r o p s b e l o w 4 0 x 1 0 9/L. Steroid
is generally avoided for the treatment of ITP
because of its immunosuppressive effect.
Zidovudine has been reported to improve
thrombocytopaenia in some patients
whereas intravenous immunoglobulin is
considered for severely symptomatic
patients with very low count. Refractory
relapsing severe thrombocytopaenia has to
be treated by splenectomy. Pneumococcal
vaccine may have to be given to these
subjects.

Anaemia i s c o m m o n i n l a t e s t a g e o f
HIV infection, which presents as anaemia of
chronic disorder. Many opportunistic
Anaemia & neutropaenia
complications and HIV itself can cause bone
* caused by HIV, secondary
marrow suppression. Anaemia with or
infections, tumours and drugs
without neutropaenia occurs in 5-10% of
* identify and treat treatable causes
patients taking zidovudine. Correction of the
* blood transfusion, erythropoietin,
primary treatable causes for anaemia is
G-CSF/GM-CSF
imperative,

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 in addition to supportive measures like blood
transfusion or erythropoietin treatment. Apart
from lymphopaenia , a m i l d d e g r e e o f
neutropaenia i s s o m e t i m e s s e e n i n p a r a l l e l
with progression to AIDS. Profound
neutropaenia is, however, often the result of
HIV-related complications or therapy. Again,
amelioration of the underlying culprit is
essential though the adjunctive therapeutic
or prophylactic use of the cytokines G-CSF
and GM-CSF in neutropaenic AIDS patients
is growing.

Endocrine and metabolic problems

Several endocrine abnormalities relating directly or indirectly to HIV infection have

been described. Potential pathogenic mechanisms include destruction of endocrine tissues
by infectious, neoplastic or haemorrhagic processes, alteration of hormonal secretion or
function by inflammatory factors, and side effects due to drugs.

T h e adrenal g l a n d i s t h e c o m m o n e s t
affected endocrine organ. Cytomegalovirus
Adrenal insufficiency in HIV infection causing adrenalitis is well
* CMV adrenalitis is the commonest recognised while disseminated
cause mycobacterial (tuberculosis and atypical)
* serum cortisol level and short infection, cryptococcus, toxoplasma,
synacthen test for diagnosis pneumocystis, lymphoma and KS can also
* hydrocortisone and fludrocortisone involve the adrenals. Involvement is usually
replacement subclinical but overt adrenal insufficiency
with clinical and biochemical changes
occurs uncommonly in severely affected
cases, especially when the patient is under
stress. Glucocorticoid with or without
mineralocorticoid replacement should then
be considered.

Thyroid f u n c t i o n i s a b n o r m a l i n s o m e
HIV-infected patients. The serum T3 level is
usually not as low as similarly ill patients
suffering from other diseases. The raised
resting energy expenditure may contribute
to the AIDS wasting syndrome, which is
different from that resulting from simple
starvation. In patients with AIDS, fat
tissue is not preferentially depleted. Instead,
patients lose muscle along with fat.

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 This loss of lean body mass has been found
to correlate inversely with survival and
Weight loss & wasting in HIV functional status. Hyperalimentation,
* caused by reduced nutrient intake, unfortunately, can only build up fat stores
malabsorption, hypermetabolism and not lean tissue in AIDS patients who are
and metabolic disturbances losing weight. Metabolic dysregulation, with
* difficult to regain after loss, more not yet clear mechanisms but possibly
so for lean tissue mediated through cytokines, may be a major
* wasting is associated with cause of the wasting. As weight and lean
morbidity and mortality muscle loss tend to occur in prominent
* minimise weight and muscle mass bouts with incomplete recovery during
loss by ensuring adequate nutrient secondary infections, it is important to
intake and treating active diseases prevent this by aggressively treating active
energetically diseases and also giving full nutritional
support (both calorie and protein) as early
as necessary. The role of anabolic agents,
cytokine-inhibitors, and exercise to replete
lost muscle mass are still experimental. The
hypertriglyceridemia characteristic of AIDS
has no correlation with the degree of
wasting.

Decreased libido and hair loss have been reported in HIV positive men. Reduced
testosterone concentrations may be found in those who have progressed to AIDS, usually
w i t h i n a p p r o p r i a t e l y l o w g o n a d o t r o p h i n l e v e l . Gonadal f u n c t i o n i n w o m e n w i t h H I V i n f e c t i o n
h a s n o t b e e n a d e q u a t e l y s t u d i e d . T h e pancreas i s a l s o v u l n e r a b l e t o o p p o r t u n i s t i c
infections, cancers, and drug toxicity in patients with HIV disease. For example,
cytomegalovirus, lymphoma, and drugs like pentamidine, didanosine and co-trimoxazole can
all cause pancreatitis with resultant permanent damage.

Cardiac, renal & rheumatological problems

Cardiac i n v o l v e m e n t i s u n c o m m o n a n d
is often subclinical in HIV infection. Likely
Cardiac lesions in HIV pathogenic processes include opportunistic
* pericarditis ± pericardial effusion infections and tumours, resulting in
* myocarditis pericardial effusion, pericarditis, myocarditis,
* endocarditis endocarditis or a combination of them. KS,
mycobacterial disease, cryptococcal and
nocardial infection can cause pericardial
disease. Lymphoma, KS, cytomegalovirus,
Toxoplasma gondii, and cryptococcus are
common causes of myocarditis and
cardiomyopathy. Non-bacterial thrombotic
endocarditis has also been reported. Direct
involvement by HIV of the heart is also
possible.

An HIV-associated nephropathy

73
 characterised by severe nephrotic syndrome
Renal problems in HIV and renal insufficiency progressing rapidly
* HIV-related nephropathy e.g. to end stage renal failure has been well
focal/global glomerulosclerosis described. The kidneys are normal in size
* sepsis, dehydration, tumour or and tissue changes include focal or global
drugs glomerulosclerosis, with mesangial deposits
of C3, IgM and sometimes IgG. It has a
predilection for black persons. Other
nephropathies, such as diffuse mesangial
hyperplasia and a variety of immune-
complex-mediated glomerulopathies may
also occur in patients with HIV. Renal
impairment in HIV-infected patients can be
the result of nephrotoxic drugs like foscarnet
and amphotericin B, disseminated infection
with direct involvement of the kidney or
septicaemic shock, intravascular volume
depletion from diarrhoea, vomiting or poor
oral intake and rarely invasion by cancer e.g.
lymphoma.

H I V i n f e c t i o n i s a l s o a s s o c i a t e d w i t h s o m e rheumatological m a n i f e s t a t i o n s . A r t h r i t i s
m a y r e s u l t f r o m a m o d i f i e d f o r m o f R e i t e r’ s s y n d r o m e , p s o r i a t i c a r t h r o p a t h y o r H I V - r e l a t e d
arthropathy. Other connective tissue disorders that have been reported include Sicca
syndrome, lupus-like syndrome, polymyositis and vasculitis. They, however, usually lack
the typical antibodies found in classical diseases.

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 4.8 Women & HIV

Although most HIV-infected adults in the world are men, women of reproductive age
are the fastest growing population to becoming infected. Globally, the ratio of male to female
HIV infection is approaching one and may soon be reversed. Epidemiologically, heterosexual
transmission followed by injecting drug use are the commonest risk factors for HIV infection
in women. In some places, AIDS is one of the leading causes of death for young women.
The understanding of HIV in women, both in clinical and social contexts, is only beginning
to receive attention. A majority of HIV positive women in the world do not have access to
optimal care and support.

Spectrum of HIV disease

75
 The natural history and clinical
manifestations of HIV infection in women
Clinical spectrum of HIV have not been as well studied as those for
Infection in women men. It is believed, however, that there is
* similar to men but less KS little gender difference with the exception of
* gynaecological lesions common - certain unique gynaecological complications
recurrent vaginal candidiasis, occurring in women. Also, KS is much rarer
cervical intraepithelial neoplasia, in women and essentially only occurs in
and carcinoma of cervix female partners of infected bisexual men.
Candida infection of the mucosa is the most
frequently observed opportunistic infection.
Vaginal candidiasis can occur at an early
stage of HIV infection. Recurrent or
refractory episodes should alert health care
workers to the possibility of an underlying
HIV infection. Genital herpes is also a
common clinical problem. Cervical intra-
epithelial neoplasia (CIN) is a disease to be
looked out for, which is related to human
papillomavirus. CIN progresses more quickly
to cervical cancer in HIV positive than HIV
negative women, especially for patients with
advanced HIV disease. The frequency of
Management
pelvic inflammatory disease and its
* physical, psychological and
complications may be higher compared with
social aspects
HIV negative people. Pregnancy does not
* treatment and prevention of
seem to hasten the progression of HIV
opportunistic infections
disease. Similarly, asymptomatic HIV-
* regular monitoring for cervical
infected pregnant women are not at an
neoplasia
increased risk for adverse outcome of
* antiretroviral therapy as
pregnancy.
indicated

Situations under which zidovudine is indicated in men also apply to women.

Previously, there has been concern about its use during pregnancy because of reports of a
slightly increased chance of foetal anaemia and growth retardation associated with
zidovudine use. However, no teratogenicity has been documented with zidovudine intake
during pregnancy, and its safety is increasingly being recognised. Pregnant mother can
possibly tolerate zidovudine well. A recent study shows that zidovudine (given before and
during delivery, as well as to the newborn for six weeks) can significantly lower the risk of
vertical transmission. The use of other antiretroviral drugs during pregnancy has not been
established at the present time.

Regimens for the treatment and prophylaxis of secondary infections in women are the
same as in male patients. Regular screening for cervical neoplasia with pap smear should be
part of the monitoring programme for an HIV positive woman. Besides clinical management,
psychosocial problems, needless to say, have to be properly addressed. To a certain extent,
women are often socially oppressed. There is also the problem that HIV positive women are

76
more likely marginalised people of the society - drug users or commercial sex workers
(prostitutes) or both and the provision of health care services to these communities requires
additional efforts. Moreover, to look after a child with HIV infection will surely add to the
burden and stress. It is clear that caring for HIV-infected women can never be
comprehensive without a good social support for their day-to-day living.

Perinatal transmission of HIV

Transmisssion of HIV from an infected

mother to her infant has become the most
Intrauterine common cause of paediatric HIV infection
Intrapartum today. The exact mechanisms have not been
Via breast milk fully elucidated. Possible times of infection
include (1) intrauterine transfer of HIV in
maternal blood across the placenta, (2)
inoculation of maternal blood and body fluid
during delivery, and (3) postnatal infection
via breast milk. The risk of vertical
transmission varies between different
studies and from country to country,
ranging from 15-20% in developed countries
to 30-40% in developing countries like those
in Africa. Advanced HIV disease, low CD4
count, p24 antigenaemia, and severe
prematurity are found to be associated with
an increased risk. Caesarean section has
been suggested to decrease transmission
risk but no definite benefit could be shown
to date.

Other HIV-related issues in pregnancy

77
 The interplay between HIV infection
and pregnancy can be complex and intricate.
HIV and pregnancy Worldwide, efforts have been made to try
* One does not adversely affect the reducing the incidence of perinatal
outcome of the other when in transmission. However, measures can only
coexistence be implemented when one knows that HIV is
* antenatal testing may be indicated complicating the pregnancy. In some places,
with full pre-test and post-test antenatal HIV testing is offered to pregnant
counselling women who or whose sex partner gives a
* HIV-infected mother should be history of higher risk behaviours. This may
counselled to make informed be valuable particularly for areas with high
decision about continuing HIV prevalence. Management of babies born
pregnancy or not to HIV-infected mother is certainly facilitated
* use of zidovudine during pregnancy by the knowledge of the HIV status. It
and delivery is safe and effective in enables the mother to benefit from active
reducing vertical transmission clinical intervention and the option of
* avoid breast feeding if possible continuing the pregnancy or not. Pre-test
counselling, however, with thorough
explanation of the implication of the test and
positive result, should be an integral part of
the testing procedure, which is conducted
voluntarily. Strict confidentiality has to be
ensured in the system.

HIV positive women should be counselled about the pros and cons of continuing or
discontinuing the pregnancy. Issues to be considered are: risk of transmission to the infant,
possible course of HIV disease in an infected child, care of the baby and family support, and
likely psychological stress from the pregnancy or its termination. Her partner may need to be
involved for making decision about the pregnancy and full support should be rendered
subsequently, where appropriate, whatever the decision is. Close monitoring of HIV status
should be continued during the pregnancy. Primary or secondary PCP prophylaxis is to be
given whenever appropriate. The use of zidovudine should be considered according to
established protocol. It should be commenced after the first trimester if indicated regarding
the woman’ s HIV disease status, or to reduce chance of perinatal transmission if pregnancy
is to be continued. High dose intravenous zidovudine is to be given during labour to
augment its protective effect, and syrup zidovudine be provided to the newborn for say,
a n o t h e r s i x w e e k s a f t e r b i r t h ( s e e “ Gu i d e l i n e s o n m a n a g e m e n t o f H I V i n f e c t i o n i n c h i l d r e n ”
by Scientific Committee of Advisory Council on AIDS, 1995). Invasive procedures such as foetal
scalp blood sampling should be avoided as far as possible to minimise the risk of
transmission during the intrapartum period. Similarly, breast feeding is not recommended if
there is availability of safe alternative - artificial milk, to minimise chance of transmission
after delivery. Following pregnancy, HIV positive women need to be further counselled
about future procreation and contraception. The condition should be kept under periodic
review. Also, there should be regular follow-up of the HIV disease.

78
 4.9 Paediatric HIV/AIDS

P r i o r t o a p p ly i n g H I V a n t i b o d y s c r e e n i n g t o d o n a t e d b l o o d a n d i n a c t i v a t i o n o f b l o o d
products by heat or detergents, transmission of HIV in children was largely through
transfusion of contaminated blood or blood products. The progression of HIV disease in
transfusion-acquired patients was fastest when the immune system was very immature (in
young child) or degenerative (in case of elderly) at time of infection and when whole blood
was received. Since mid 1980s, transfusion-related HIV infection has become exceedingly
rare in countries where appropriate measures for safeguarding blood and blood products
were adopted, including Hong Kong. Perinatal transmission (mother to infant) has then
emerged as the major cause of HIV transmission in children.

Clinical manifestations

Children with perinatally-acquired HIV

infection has in general a faster rate of
HIV-related manifestations in disease progression than adults. 20 to 30%
babies born to HIV positive of those with early onset develop AIDS by
mothers the age of one, whereas the rest has a later
onset and less rapid disease progression.

Highly suggestive of HIV infection Due to the diagnostic difficulty and different
* Pneumocystis carinii p n e u m o n i a spectrum of clinical presentations compared
* lymphoid interstitial pneumonia with adults, the Centers for Disease Control
* oesophageal candidiasis or and Prevention (CDC) has proposed a
persistent oral candidiasis separate classification system for HIV
* parotitis infection in children under 13 years old,
which was revised in 1994 (Appendix V).

Suggestive of HIV infection Clin i c a l l y , HIV-infected children can

* recurrent severe bacterial infections present with non-specific systemic features
* failure to thrive and chronic such as failure to thrive, fever, generalised
diarrhoea lymphadenopathy and hepatosplenomegaly.
* encephalopathy & developmental Chronic diarrhoea can result from enteric
delay or regression infections, HIV enteropathy and
* hepatosplenomegaly & generalised disaccharidase deficiency. Frequent, slowly
lymphadenopathy responsive bacterial infections e.g. otitis
media and pneumonia, are clues to the
underlying immunodeficiency. The presence
of Pneumocystis carinii pneumonia, lymphoid
interstitial pneumonia ( a chronic pneumonia
with progressive alveolocapillary block),
persistent oral candidiasis, disseminated
CMV infection or

79
 non-suppurative parotitis clearly warrants
an HIV antibody test. Neurological
involvement is common in advanced HIV
disease. This is usually manifested as
developmental delay, loss of milestones and
features of encephalopathy.
Cardiomyopathy and nephropathy can also
occur. Paediatric AIDS patients usually run
a rapidly downhill and fatal course,
particularly when complication like
Pneumocystis carinii pneumonia has
developed.

Laboratory findings and diagnosis

With clinical suspicion of an underlying HIV infection, the diagnosis should be

confirmed by laboratory tests as there are other causes of immunodeficiency, albeit
uncommon, in infancy. The HIV antibody test in the first 18 months of life is by itself
insufficient for diagnosis due to the presence of maternal antibody.

Other tests of different sensitivity and

specificity have been used in the diagnosis
Diagnostic tests for perinatal of perinatally acquired HIV infection. Viral
HIV infection culture remains the gold standard though it
is not 100% sensitive in early infancy, and

Definitive the test is both technically difficult and not

* positive HIV viral culture readily available. Serum p24 antigen is
* positive PCR for viral genome specific but it is only moderately sensitive.
* positive p24 antigenaemia Polymerase chain reaction (PCR) is a
* positive HIV antibody after 18 sensitive and promising method. In this
months old technique, the proviral DNA or viral RNA in
lymphocytes is enzymatically amplified. PCR

Suggestive is, however, not optimally sensitive in the

* lowered CD4 level, CD4 to CD8 first 2 months of life and it carries the
ratio potential inherent pitfall of false positivity.
* Hyper- or hypo- Detection of anti-HIV IgM and IgA have
gammaglobulinaemia also been researched on in some occasions.
* elevated serum β2 - m i c r o g l o b u l i n Children with positive HIV antibody at birth
but who subsequently revert to negative
and neopterin level
status still need follow up to ensure that
they are not infected.

80
 Similar to adults, surrogate markers are useful clues to diagnosis, and serve as guides
to management of HIV infection in children. CD4 cell is the main target of HIV and its count
demands regular monitoring. It should be noted, however, that infants have a higher
baseline CD4 count than adults. A different reference range is needed. Besides a lowered
CD4 level, a reduced CD4 to CD8 ratio is also a common indicator of the underlying disease
process. Serum β2- m i c r o g l o b u l i n and neopterin may be raised. Polyclonal

hypergammaglobulinaemia or hypoglobulinaemia may be present. Cell-mediated immunity

may be abnormal, as well as the antibody response to vaccines or infections.

Management

Regular monitoring of the disease

Management of HIV-infected status, early recognition and treatment of
Children complications, appropriate antiviral therapy
* early diagnosis of HIV infection and prophylaxis for infections, and
* PCP prophylaxis as indicated meticulous attention to psychosocial and
* antiretroviral therapy for AIDS developmental needs are essential
and prominent symptoms components in the management of children
* vigorously treat active infections with HIV/AIDS. It is crucial to remember that
* full nutritional support the medical, psychological and social
* prevent secondary infections as problems of the HIV-infected mother, or
necessary both parents, may greatly hamper the
* immunisation with fine adjustment provision of necessary care and treatment
in scheme for the child. The management plan should
* ? immunoglobulin therapy be individually designed, taking into
* allow full physical, social and consideration the unique situation faced by
emotional development the patient and his family.

A high index of clinical suspicion is

prudent. HIV diagnosis can be difficult in
early infancy, but delayed diagnosis often
leads to even more problems with high
morbidity and mortality. As in adults,
prophylaxis against PCP is a cornerstone for
managing paediatric HIV infection. However,
implementation can be difficult as the
majority of PCP occurs before the age of one
when the diagnosis of HIV may still be
unclear. In 1995, CDC has recommended PCP
prophylaxis for all HIV exposed infants from
age 4-6 weeks to 4 months, and to HIV-
infected or indeterminate children from age 4
to 12 months. For HIV positive children
older than 1 year, prophylaxis is given for
those

81
 with a low age-specific CD4 count or
percent. Lifelong prophylaxis is needed for
previous episode of PCP. Co-trimoxazole
thrice weekly is the preferred regimen. It may
also protect against recurrent bacterial
infections.

Secondary prevention of opportunistic

infections (e.g. candidiasis and
toxoplasmosis) is necessary to prevent
relapse. Intravenous immunoglobulin has
been shown to reduce the incidence of
bacterial infections in children with a
relatively high CD4 level. It may also be
recommended for use in patients with severe
immune thrombocytopaenic purpura
unresponsive to zidovudine, and
hypogammaglobulinaemia with recurrent
bacterial infections.

Antiretroviral therapy with zidovudine

should be used when the child develops
Antiviral therapy AIDS or suffers from major symptoms
* zidovudine is the first line drug referable to HIV infection. A higher dose
* ? ddI/ddC relative to size or body weight is prescribed
* ? combination therapy in paediatric patients, especially when
neurological manifestations are prominent.
Close monitoring for side effects e.g.
neutropaenia and anaemia, which can be
delayed, is necessary. The role of
didanosine (ddI) and dideoxycytidine (ddC)
have not been established although it seems
reasonable to use them at least in cases of
zidovudine intolerance or failure.

Supportive measures such as adequate

nutritional supplementation, maximal
correction of malabsorption, control of
Immunisation
chronic diarrhoea and aggressive treatment
* measles-mumps-rubella (MMR)
of secondary infections are all important to
vaccine is safe
maintain health as far as possible.
* BCG is safe for asymptomatic
Immunisation scheme has to be adjusted
children
due to the immunosuppression. Live
* inactivated (Salk) poliomyelitis
vaccines should be avoided except that for
vaccine preferred
measles. BCG should not be given to
* ? pneumococcal and influenza
symptomatic children. If available,
vaccines
inactivated (Salk) poliomyelitis vaccine

82
 shall be used in place of live oral (Sabin)
vaccine as the latter may still be excreted for
many months in the stool of immunised
infants. Even if vaccinated against certain
disease, the protection can never be
assumed to be complete for patients with
HIV infection.

HIV-infected children should be allowed to lead a o r m a l” s o c i a l l i f e a s p e r m i t t e d b y

their health status. The adoption of universal precautions for infection control is adequate
for preventing the already extremely low risk of HIV transmission in day-to-day interaction,
including the setting of institutions like day care centre. Like adults, HIV status is treated in
strict confidence and should only be revealed on a eed-to-know” basis. In addition, the
family has to be offered full support to cope with not just the disease but the stigma.

83
 4.10 Idiopathic CD4+ T-lymphocytopaenia

S i n c e 1 9 8 9 , s e v e r a l i n v e s ti g a t o r s i n t h e
world have independently reported cases of
ICL CD4+ T-lymphocytopaenia with
*not new; rare, heterogenous disease opportunistic infections or Kaposi's sarcoma
*not caused by a virus but no evidence of HIV infection. The
*progressive CD4 depletion phenomenon caused much public concern,
uncommon notably during the VIIIth International
Conference on AIDS in July 1992 in
Amsterdam, when the media reported the
development of a potential epidemic of a
new viral AIDS-like disease. Extensive
investigations by the World Health
Organization and the Centers for Disease
Control later concluded that there was no
evidence for a new epidemic. The syndrome
has probably been in existence for a long
time, and only become apparent with the
wider availability of CD4 count testing.

For surveillance purpose, a provisional case definition was devised by the CDC for
suspected cases during the global investigative exercise: (a) a documented absolute CD4+
T-lymphocyte count of less than 300/ul or less than 20% of total lymphocyte on more than
one occasion; (b) no serologic evidence of HIV infection and (c) no defined
immunodeficiency or therapy associated with T cell depletion. In June 1993, the CDC
reported that a total of 125 cases have been cumulated in USA, including 14 children. The
term "Idiopathic CD4+ T-lymphocytopaenia (ICL)" was used by some researchers during the
investigation.

It is now generally agreed that ICL represents a demographically, clinically,

immunologically and epidemiologically heterogenous group of diseases that are unlikely to
be caused by a retrovirus or other transmissible agent. The condition is distinctly rare
despite the extensive search undertaken. Unlike that of HIV infection, the male-to-female
ratio is generally lower. Some children have also been affected by the condition.
Opportunistic infections similar or dissimilar to those related to HIV infection can occur
among ICL patients. In a series, some 40% had AIDS-defining diseases. However, in
contrast to HIV infection, progressive CD4 depletion is uncommon and patients usually
remain clinically stable. Evidence suggested that opportunistic infection generally resulted
from rather than induced the ICL-related immunosuppression.

84
 5. MANAGEMENT OF ADULT HIV INFECTION

5.1 General management & treatment of

common complications

The clinical management of HIV infection encompasses many components. They are
(1) optimisation and maintenance of health, (2) regular monitoring for HIV disease
progression, (3) prophylaxis of opportunistic infections, (4) early diagnosis and aggressive
treatment of HIV-related complications, (5) antiretroviral therapy, (6) psychosocial support
for the patients and their families/partners and (7) prevention of future HIV transmission.
This section deals with the general aspects on health maintenance, antiviral therapy and
outlines the recommended protocols on treatment and prevention of common secondary
infections and neoplasms. The other aspects of the management are covered in details
elsewhere in the manual.

General management - nutrition, lifestyle modification and others

T h e l o n g l a t e n c y of H I V i n f e c t i o n i m p l i e s t h a t a g r e a t m a j o r i t y o f i n f e c t e d p e o p l e
remain largely asymptomatic for a prolonged period of time. The objective of management at
this level is to, as far as possible, maintain optimal health. Apart from intercurrent infections,
other factors which may be important in affecting the course of the disease are nutrition,
stress, smoking, co-infection with sexually transmitted diseases, extra or new HIV load, use
of illicit drugs and the availability of psychosocial support. Obviously, refraining from the
potential risk factors means a change in lifestyle. In this regard, information, education, peer
support and other backup services have to be offered as necessary. A good patient-carer
relationship is essential and the client should be encouraged to play an active and
responsible role in the overall management of his/her infection and its related problems. A
positive but realistic approach towards the positive status is probably the best way to go
by.

85
 Although there is no evidence that
nutritional intervention can reverse the
immune dysfunction due to HIV, it is
possible however that poor nutrition can
Nutrition in HIV disease precipitate or aggravate secondary
* malnutrition is common which infections. It has been suggested that
can significantly affect the quality nutritional status as reflected by lean body
of life and survival mass is a significant determinant of survival
* nutritional assessment and in patients with AIDS. Intake of adequate
support is prudent, especially in and nutritious food should be emphasised
advanced stage of HIV infection starting from the asymptomatic stage and
* input from dietitian with dietary should be continued throughout the course
manipulation and supplementation of HIV disease. Nutritional assessment and
as necessary dietary advice from dietitian may be
necessary. Several parameters can be used
to assess the nutritional status, e.g. body
weight, % of loss from usual body weight,
body mass index, triceps skin fold and mid-
arm circumference, and also biochemical
data like that of serum albumin level. Serial
readings are more informative than isolated
single values.

When HIV disease progresses with the emergence of anorexia, weight loss, chronic
diarrhoea, malabsorption or other opportunistic complications, nutritional support becomes
an increasingly important part of the management plan. In tackling some specific problems in
the course of the disease, dietary manipulation can be a useful adjunct, e.g low-fibre, low-fat
and low-residue diet is required for patients with chronic diarrhoea resulting from enteric
infections. Nutritional supplementation through enteral or even parenteral feeding may be
used as necessary at times of poor oral intake, especially when there is concurrent active
major infections or malignancies.

86
 T h e m e ri t s o f h e a l t h y l i f e s t y l e a p p l y
equally well to people with HIV infection.
Healthy lifestyle Appropriate exercise can upkeep one’ s
* refrain from smoking and health status if it is undertaken consistently
recreational drugs and regularly. HIV positive persons should
* safer sex practice be encouraged to have daily exercise that is
* avoid stress and overworking, physically and socially affordable. Though
maintain good mental health poor mental health with, for instance,
* regular exercise and adequate rest depression or anxiety, may not adversely
affect disease progression, it is reasonable
to include maintenance of healthy mental
state in the management plan. Social
stigmatisation, disturbed relationship with
partner or family, personality problem with
difficulty in coping with the disease may all
contribute to upsetting one's mental health.
Besides psychosocial support, counselling
and psychotherapy, drugs are needed in
case of overt psychiatric disorders e.g. major
depression.

Smoking has been suggested to be associated with a faster rate of progression of HIV
disease. Contracting sexually transmitted diseases e.g herpes simplex infection, infection by
a new and/or different HIV strain, use of recreational drugs may also adversely affect the
outcome. The avoidance of these 'risk' factors may demand change of certain behaviours
that have already been 'deep-seated' for a long time. Efforts should be made to educate and
offer support for the necessary behaviour changes. The aim shall be to reduce the harm if
they cannot be avoided in total. For example, cigarette consumption is to be reduced if to
quit smoking is not feasible in the meantime. Realistic and individualised advice for adopting
and maintaining safer sex practice is beneficial for the client and also helps in preventing
further spread of HIV in the community.

At some stage, HIV-infected patients may seek alternative or complimentary medicine

for their treatment. This is understandable as they are faced with a progressively serious and
life-threatening disease that has no cure at present. There is a wide range of alternative
therapy options which include (i) non-pharmacological modalities like meditation,
aromatherapy, massage, yoga and (ii) drugs such as compound Q, coenzyme Q10 and
astragalus, just to quote a few examples. The efficacy of these measures have not been
proven scientifically. Sometimes, toxic agents or bizarre ways of administrating the treatment
can be potentially harmful to the patients. It is crucial, however, that an informed and
thorough discussion between a health care provider and the patient be held, rather than
outright rejection of alternative therapies. Dealt with improperly, the issue may become a
trigger in alienating the patient and compromising patient-carer relationship. This may in
turn deny the patient benefits that conventional care can offer.

87
Treatment and prophylaxis of common HIV-related diseases

Opportunistic complications,
especially infections, remain the leading
Treatment of HIV-related cause of morbidity and mortality in patients
Opportunistic infections with HIV infection. In addition to
* effective agents available for antiretroviral therapy, treatment and
most diseases prophylaxis of secondary infections is the
* major factor in determining the mainstay of medical management. Based on
quality of life and survival of new knowledge and application of standard
patients with HIV/AIDS as well as newer antimicrobials, better
* chronic maintenance therapy treatment outcome has become evident in
often necessary to prevent the recent years. Maintenance treatment
relapse or suppress the infection (secondary prophylaxis) of many
opportunistic infections is necessary as it is
usually impossible to eradicate the
pathogens in the milieu of a defective
immune system. The role of primary
prevention is investigated and PCP
prophylaxis is a brilliant example of the value
and success of this approach.

As antibiotic prophylaxis becomes

commonly used, more problems arise, e.g.
drug interactions between prophylactic and
Primary prophylaxis of HIV-
antiviral agents, cost and cost-effectiveness,
Related opportunistic infections
patient compliance, drug intolerance and
* logical approach as effective
development of pathogen resistance. The
prevention may significantly reduce
possibility of multiple opportunistic
ensuing morbidity and mortality
pathogen prophylaxis (MOPP), an approach
* PCP prophylaxis has become part
which works by using broad spectrum
of standard care for indicated
antimicrobials, may help alleviating some of
patients
these problems. Also, continued effort in
* consider toxicity, drug interactions,
developing new, more effective and less
efficacy, cost-effectiveness, patient
toxic antimicrobial agents is necessary to
compliance and drug resistance
combat resistant and new infections. In the
meantime, the prescription of prophylactic
drugs has to be considered after balancing
its potential risks with benefits. Some of the
determining factors are drug toxicity,
efficacy, cost, convenience of administration
and acceptance by patients.

88
Disease Drug Duration Comment/Side
effects

Bacillary 1. Erythromycin 500mg 4 weeks for skin For relapse, give 3

Angiomatosis 4 times/D OR disease months' treatment or
2. Doxycycline 100mg/D 6 weeks for continuous
3. *Co-trimoxazole, visceral disease, suppressive therapy
* Rifampicin ?lifelong
therapy

Candidiasis 1. Amphotericin B lozenge Till lesions clear Deranged liver

Oral or solution or topical function is more
miconazole 4 times/D common with
2. Ketoconazole 200mg/D 7 days ketoconazole
Fluconazole 50mg/D
Itraconazole 100mg/D Itraconazole and
ketoconazole
require acid for
absorption

Oesophageal Ketoconazole 200-400mg/D 21 days Recurrent

Fluconazole 100-200mg/D candidiasis may
Itraconazole 100-200mg/D require
maintenance therapy
e.g. fluconazole 50-
100mg daily or 3
times per week

Refractory
candidiasis may
need IV
Amphotericin B

* investigational approach/regimen

89
Disease Drug Duration Comment/Side
effects

Cryptococcosis
Treatment 1. Amphotericin B
0.5-0.8mg/kg/D ± 5FC
2. Fluconazole 400mg/D
Maintenance 1. Fluconazole 200mg/D
2. Amphotericin B 1mg/kg
per week
3. *Itraconazole
* primary *Fluconazole 50-200mg/D
prophylaxis
8-10 weeks in Amphotericin B for 2
total weeks followed
by fluconazole
should be the right
treatment for most
patients
lifelong
Renal impairment,
nausea, fever, chills,
hypokalaemia and
bone marrow
suppression are
possible side effects
of Amphotericin B

Cryptosporidiosi 1. *Paromomycin 500mg Depends on Gastrointestinal

s 4 times/D Response upset is the side
2. *Spiramycin effect with these
3 megaunit drugs, hearing loss
3 times/D can occur with
3. *Azithromycin azithromycin
1200mg/D
Antidiarrhoeal
agents e.g. codeine
phosphate,
diphenoxylate,
loperamide are used
for chronic diarrhoea

* investigational approach/regimen

90
Disease Drug Duration Comment/Side
effects

Cytomegalovirus
Disease
Treatment 1. Ganciclovir 5mg/kg 21 days Bone marrow
twice/D toxicity especially
2. Foscarnet 60mg/kg leucopaenia, and
3 times/D phlebitis are side
(adjust dose for both drugs effects of
if renal impairment) ganciclovir

Maintenance 1. Ganciclovir 5-6mg/kg/D lifelong as Foscarnet may

5 times per week tolerated to delay cause renal
2. Foscarnet 90mg/kg/D progression or impairment,
5 times per week relapse anaemia,hypo/
*oral ganciclovir hyper-calcaemia,
1500mg/D thrombophlebitis
and
* primary @v a l a c i c l o v i r , @o r a l hypomagnesaemia
prophylaxis foscarnet,
@m o n o c l o n a l o r@p o l y c l o n a l Maintenance
immunoglobulins, therapy is indicated
*oral ganciclovir for retinitis,
neurological and
recurrent disease;
permanent central
venous access may
be warranted

Herpes simplex Acyclovir po 200-400mg 5-7 days Frequently relapsing

5 times/D disease may need
maintenance
acyclovir
(600-800mg/D)

Herpes zoster Acyclovir po 400-800mg 7 days Good response but

5 times/D or IV 5-10mg/kg relapse may
Q8H occur

Isosporiasis Co-trimoxazole 960mg 10-21 days

4 times/D

* investigational approach/regimen
@ experimental drug

91
Disease Drug Duration Comment/Side
effects

Kaposi's sarcoma 1. local vinblastine Depends on Vincristine +

injection Response and bleomycin is
2. local irradiation Tolerance, minimally myelotoxic
3. systemic chemotherapy usually
with e.g. vinblastine, Every 2-3 weeks
vincristine+bleomycin ± For
adriamycin chemotherapy

Lymphoma
Primary CNS Radiotherapy

Systemic Systemic chemotherapy e.g. The dose and

non-Hodgkin's regimen of CHOP strength of systemic
(cyclophosphamide, chemotherapeutic
epirubicin, vincristine and agents may need to
prednisolone) or M-BACOP be adjusted
(methotrexate,
bleomycin,epirubicin,
cyclophosphamide
vincristine and
prednisolone)

Microsporidiosis 1. *Metronidazole 400mg Depends on Albendazole may be

3 times/D Response useful for the
2. *Albendazole 400mg species Septata
twice/D intestinalis

Molluscum 1. liquid nitrogen Condition tends to

Contagiosum 2. electrical curettage recur

* investigational approach/regimen

92
Disease Drug Duration Comment/Side
effects

Mycobacterium
Tuberculosis
Treatment Four drugs combination of Four drugs for 2 Monitor for
Isoniazid 300mg/D months, then hypersensitivity
Rifampicin 450-600mg/D continue reaction, liver
Pyrazinamide 1.5-2g/D isoniazid and toxicity, peripheral
Ethambutol 20mg/kg/D rifampicin for at neuropathy and
+ Pyridoxine 10-50mg/D least 9 months optic neuritis

Disseminated TB Prophylaxis has been

may need 12-18 proposed using
Months' INAH alone or with
treatment or more rifampicin in
overseas studies
Mycobacterium
Avium complex
Treatment Combination regimen of 3-4 Lifelong Suppressive
drugs : treatment to
Clarithromycin 500mg decrease
2X/D bacteraemia and
Ethambutol 20mg/kg/D symptoms
Rifabutin 450mg/D
Clofazimine 100mg/D In-vitro sensitivity
(Ciprofloxacin , rifampicin, not correlate with
amikacin and*azithromycin clinical response
are used less commonly) except for
clarithromycin

Monitor for
gastrointestinal
upset, liver
impairment, low
blood counts, optic
neuritis and tissue
pigmentation
Primary *Rifabutin, Clarithromycin
Prophylaxis

Oral hairy Acyclovir 200-400mg 10-14 days Lesion usually

Leucoplakia 5 times/D or simply recurs after stopping
observe acyclovir

* investigational approach/regimen

93
Disease Drug Duration Comment/Side
effects

Penicilliosis
Treatment Amphotericin B Few reports
0.5-0.8 mg/kg/D for 4 regarding optimal
weeks, followed by treatment and
itraconazole 400mg maintenance
twice/D for 3 months regimens

Maintenance Itraconazole 400mg/D Lifelong

Pneumocystis
Carinii
Pneumonia
Treatment 1. Co-trimoxazole IV/po
(20mg/kg/D TMP) in
four divided doses
2. Pentamidine IV
4mg/kg/D
3. Atovaquone 750mg
three times/D (mild to
moderate cases)
4. *Dapsone (100mg/D) +
trimethoprim
(20mg/kg/D in 3-4
divided doses)
5. *Primaquine (15mg/D)
+ clindamycin (450-
600mg 4 times/D)
6. *Trimetrexate IV
4 5 m g / m 2/ D w i t h
leucovirin
21 days Co-trimoxazole is the
preferred regimen if
patient can tolerate,
but its use is
associated with high
frequency of adverse
effects e.g.
hypersensitivity rash
and fever, nausea,
vomiting, liver
toxicity
For severe PCP with
pO2 <70mm Hg,
adjunctive
prednisone within 72
hours of starting
anti-PCP therapy will
reduce death
(40mg twice/D for 5
days, 20mg twice/D
for 5 days, 20mg/D
for 11 days, then tail
off rapidly)

* investigational approach/regimen

94
Disease Drug Duration Comment/Side
effects

Intravenous
pentamidine can
cause hypotension,
pancreatitis,
hypoglycaemia,
hyperglycaemia,
renal impairment and
marrow toxicity

Prophylaxis 1. Co-trimoxazole po Lifelong Co-trimoxazole is the

160mg TMP/D or three best drug, which
times per week also protects against
2. Pentamidine toxoplasmosis
(inhalational or IV)
300mg per month Aerosolised
3. *Dapsone 100mg 3 pentamidine is
times per week or daily related to
4. *Dapsone (200-300mg extrapulmonary
per week) + pneumocystis carinii
pyrimethamine infection, apical
(50-75mg per week) chest X-ray changes
5. *Pyrimethamine (50mg and bronchospasm
per week) + sulfadoxine
(1000mg per week) Dapsone can cause
6. *Trimethoprim- allergic rash, fever,
dapsone, *clindamycin- nausea, haemolytic
primaquine, anaemia, methae-
*atovaquone moglobinaemia

Progressive * Cytosine arabinoside IV Depends on

Multifocal or intrathecal Response and
Leucoencepha- Tolerance
Lopathy

Seborrhoeic Topical hydrocortisone ± Till lesions clear Severe cases may

Dermatitis antifungal agent e.g. require more
imidazole potent topical
steroid or systemic
antifungal drugs and
steroid

* investigational approach/regimen
@ experimental drug

95
Disease Drug Duration Comment/Side
effects

Shigellosis, Quinolones e.g 10-14 days Recurrent salmonella

Salmonellosis & ciprofloxacin 750mg septicaemia may
Campylobacter twice/D require maintenance
Enteritis norfloxacin 400mg therapy
twice/D

Toxoplasmosis Sulfadiazine plus

Treatment 1. Sulfadiazine IV/po 3-6 weeks pyrimethamine
(1-1.5g 4 times daily) + is the recommended
pyrimethamine (100mg regimen
on D1, then 50-75mg/D)
2. Clindamycin IV/po Pyrimethamine is
(600-1200mg associated with bone
4 times/D)+ marrow suppression
pyrimethamine (dose-related,
3. *Atovaquone 750mg reduced by giving
four times/D folinic acid 10mg
4. *Azithromycin daily), rash and liver
(1200mg daily) or toxicity
*Clarithromycin
(2g daily) plus Sulphadiazine can
pyrimethamine cause rash, drug
5. @ I n t e r f e r o n -γ and fever, nausea,
@i n t e r l e u k i n - 2 as vomiting
adjuvant therapy
Clindamycin can
cause diarrhoea,
nausea, rash, and
rarely pseudo-
membranous colitis

Corticosteroid may
be used to reduce
severe cerebral
oedema

* investigational approach/regimen
@ experimental drug

96
Disease Drug Duration Comment/Side
effects

Maintenance Pyrimethamine (25mg/D) + Lifelong

sulphadiazine/clindamycin
(half the treatment dose) +
folinic acid

* primary 1. Co-trimoxazole
prophylaxis 2. *Dapsone (200mg) plus
pyrimethamine 75mg
per week

* investigational approach/regimen

97
 5.2 Antiretroviral therapy

Human immunodeficiency virus

progressively destroys the immune system
of infected patients, predisposing them to
opportunistic infections and tumours. The
treatment and prophylaxis of these
complications are indisputably the most
important part of clinical HIV/AIDS
management. Nonetheless, it will be far more
effective if one can eradicate or control the
primary cause (HIV) of the problem.
Antiviral drugs were developed with these
aims to act directly against HIV.
Unfortunately, this approach is only met
with limited success to date.

The replicative cycle of HIV has

actually been well-delineated. Some key
Possible target sites of HIV life steps of the cycle are potential targets for
Cycle and antiviral agents attack with pharmaceutical agents. They
include (i) penetration of HIV into CD4 cell,

Viral penetration & uncoating (ii) reverse transcription of HIV RNA into
CD4 analogues, HIV-antibodies, and DNA, (iii) subsequent transcription of viral
Vaccines mRNA from proviral DNA and (iv) the final
stage of assembly and release of viral

Reverse transcription particles from infected cells. In fact, many

Nucleoside analogues e.g. AZT, drugs with different mechanisms of action
ddI and ddC, and non-nucleoside have been tested in vitro. Some of these
analogues e.g. nevirapine laboratory-potent drugs were then evaluated
in patients by going through the different

Transcription & translation phases of clinical trials. Not uncommonly,

Tat inhibitors, interferons, agents that are active in vitro a r e n o t p r o v e n
Glycosylation inhibitors, and to be effective in vivo. W i t h t i m e , h o w e v e r ,
Antisense oligonucleotides more promising new agents are being
introduced into clinical practice. To date, all

Assembly & release the registered antiviral drugs belong to the

Interferons, protease inhibitors group of non-nucleoside reverse
and immune-based therapies transcriptase inhibitors - some examples are
zidovudine (AZT, ZDV), didanosine (ddI)
and zalcitabine (ddC). Reverse transcriptase
inhibitors have remained the standard
antiretroviral drugs for HIV infection in
current clinical practice.

98
Zidovudine

Zidovudine is the first and the most

Zidovudine use in AIDS or
Advanced ARC
* prolonged survival
* reduced HIV symptoms
* weight gain
* less opportunistic infections
* better cognitive function
* improved CD4 count and
skin-test reactivity
widely used antiviral drug for HIV/AIDS. It
acts by inhibiting reverse transcriptase, the
enzyme required for transformation of viral
RNA into DNA before the latter becomes
integrated into the host genome. Clinical
studies demonstrated its effects of reducing
the incidence of opportunistic infections,
improving general being, increasing body
weight, giving greater functional capacity
and improving survival in patients with
AIDS or advanced AIDS related complex.
Zidovudine was approved by the Food and
Drug Administration (FDA) of the United
States in 1987. Very soon afterwards,
zidovudine became available for use in Hong
Kong in late 1987.

The indication of zidovudine use was

later extended to symptomatic HIV positive
patients, when it was shown to delay the
development of AIDS, though with no
Indications of zidovudine
survival benefit. Controversy and confusion
* symptomatic HIV positive
arose as to the best time to institute
patients including AIDS
zidovudine therapy when the patient was
* asymptomatic patients with
asymptomatic. An earlier study has shown
CD4 count <200/ul
that early zidovudine for asymptomatic
* ? asymptomatic patients with
patients with CD4 count <500/ul could slow
CD4 count of 200-500/ul
the progression to AIDS. However, the
Concorde trial has failed to show any
significant advantage of early versus
deferred treatment for asymptomatic HIV-
infected patients after three years of follow-
up. Nevertheless, it appears effective in
prolonging the asymptomatic (or mildly
symptomatic) period rather than extending
the time between AIDS and death.

99
 The potential benefits of zidovudine in
Toxicity of zidovudine HIV positive patients could be offset by its
* anaemia, leucopaenia and rarely toxicity. Side effects of zidovudine include
thrombocytopaenia an early occurrence of gastrointestinal upset
* nausea, vomiting and anorexia with nausea, vomiting and anorexia, and
* myalgia and myositis bone marrow toxicity which often present
* malaise, insomnia and headache later. Even though the incidence of anaemia
* rash and leucopaenia has been reduced by the
* liver derangement lower dose (500-600mg/day) used
nowadays, these adverse effects may be
disturbing to some patients, particularly with
prolonged administration. Use of zidovudine
is also associated with rash, headache,
insomnia, myalgia, myopathy and deranged
liver function. When used in HIV-infected
children, bone marrow suppression may also
occur, albeit a better tolerance than in
adults. Zidovudine therapy in children has
been reported to lead to weight gain and
improvement in cognitive function as well as
immunological and virological markers.

Apart from the pitfall of potential

toxicity, long-term zidovudine therapy
inevitably results in diminishing efficacy.
This occurs after a mean of 12-18 months of
Transient efficacy of zidovudine
benefits (longer when started in patients
* ?viral drug resistance
with early disease). The transitory clinical
* ?syncytium-inducing strains
benefit of zidovudine monotherapy may be
* ?increased viral load
related to the emergence of resistant HIV
strains as the disease advances, upsurge of
the more virulent syncytium-inducing
phenotypes, increased viral burden from
loss of immune control over viral replication,
or a combination of these factors. The
clinical importance and relative contribution
of each of these mechanisms are not
thoroughly understood yet.

Didanosine & zalcitabine

Didanosine or zalcitabine is prescribed when there is zidovudine intolerance or failure.

Didanosine was approved by the FDA in 1991 as an agent for monotherapy in advanced
HIV infection. It was based on research findings that its use could result in weight gain,
improvement of immunological markers (CD4 count and skin hypersensitivity reactions), and
decrease in virological markers (p24 antigenaemia). In a later trial, it was demonstrated that
switching to didanosine after 8 to 16 weeks of zidovudine was associated with a slower
progression to new AIDS-defining illnesses and death. While there is likely benefit for
patients by switch of therapy, no firm recommendation can yet be made on the best time for
changing over. Similar to zidovudine, resistant strains to didanosine emerged after

100
prolonged therapy. Interestingly enough, the resistance of some zidovudine-resistant
strains was reportedly reduced by a didanosine resistance mutation.

Zalcitabine was approved by the FDA in 1992 for use in combination with zidovudine
in treating advanced HIV disease with clinical or immunological deterioration. This was
based on a trial which demonstrated improvement of immunological and virological markers
with the combination regimen. A recent study showed that zalcitabine monotherapy was at
least as effective as didanosine in a group of patients with advanced disease, and possibly
carried a slight survival benefit. Resistance to zalcitabine has also been reported and there
could be cross-resistance with didanosine.

Didanosine and zalcit abine have a

Didanosine different spectrum of adverse effects
* simultaneous intake of two tablets compared with zidovudine. Pancreatitis and
for buffer against gastric acid painful peripheral neuropathy are their main
* taken 1 hour before or 2 hours toxicities. While pancreatitis (5-10%) is more
after meal, with tablets crushed, common with didanosine, peripheral
chewed or dispersed in water neuropathy (7-29%) occurs more frequently
* toxicity of diarrhoea, pancreatitis, in patients taking zalcitabine. Lethal
hyperamylasaemia and peripheral pancreatitis has been reported with the use
neuropathy of didanosine and it is important to regularly
monitor clinical symptoms and serum
amylase level. Clinical benefit of didanosine
may also be limited by its inconvenient
administration - taking two big tablets and
Zalcitabine
with an empty stomach - which can
* administration easier than ddI
substantially affect the patients ’ acceptance
* toxicity of peripheral neuropathy,
and compliance. The neuropathy is
rash, stomatitis and pancreatitis
characterised by numbness, tingling and
pain in distal extremities, more often in
patients with history of neuropathy or intake
of other neurotoxic drugs. Its incidence is
related to the daily and cumulative dose of
zalcitabine or didanosine used. Diarrhoea is
common with didanosine but symptoms are
usually mild and easily controllable. Other
side effects of zalcitabine include skin rash
and stomatitis, which may subside despite
continued therapy.

101
Other antiretroviral agents

Although zidovudine, didanosine and zalcitabine are useful drugs in suppressing HIV
replication, they are by no means effective in controlling the infection. Acting as reverse
transcriptase inhibitors, they cannot inhibit viral replication in chronically infected cells
harbouring HIV genome. Other newer agents are being actively developed and tested for
safety, toxicity and efficacy. Various drugs with different sites of action have come into
place recently. The better known or promising ones are non-nucleoside reverse transcriptase
inhibitors, inhibitors of TAT (transactivator of transcription) protein, protease inhibitors and
glycosidase inhibitors. Newer nucleoside analogues, e.g. stavudine (d4T) and lamivudine
(3TC) have also been studied.

Stavudine h a s b e e n a p p r o v e d b y t h e F D A i n 1 9 9 4 f o r u s e i n p a t i e n t s w i t h a d v a n c e d
HIV disease who are intolerant of other approved antivirals, or when the latter fail. The
benefit shown to date is, however, only with the surrogate markers. Peripheral neuropathy
(15-21%) is the main limiting toxicity. Raised transaminase level can also occur. No cross
resistance with AZT has been demonstrated for d4T.

Lamivudine h a s b e e n r e s e a r c h e d f o r u s e i n c h r o n i c h e p a t i t i s B i n f e c t i o n w i t h s o m e
preliminary positive effects. Its anti-HIV activity is synergistic with zidovudine in in vitro
condition. Recently, this synergistic effect was also demonstrated in clinical trials which
showed sustained and greater improvement in CD4 level as well as viral load (follow-up for
24 weeks) when compared with zidovudine monotherapy. Whether this encouraging
immunological and viral results can be translated into clinical benefit is not known.
Nevertheless, lamivudine apppears to be a promising agent for use in combination antiviral
therapy.

Non-nucleoside analogues, e.g. nevirapine , a r e e x t r e m e l y s p e c i f i c a n d p o t e n t f o r

inhibiting HIV-1 replication. Except for some dose-limiting rash, it is generally well tolerated
with low toxicity. Unfortunately, there is rapid development of drug resistance. Nevirapine
may therefore only be potentially useful in combination therapy and not monotherapy. The
tat inhibitors target HIV at the midpoint of its replicative cycle by interfering with the gene
product needed for transcription of proviral DNA into viral mRNA. The initial result of this
group of drugs has been disappointing.

In some pilot studies, protease inhibitors, either used singly or in combination with
zidovudine, appear to be potent and safe. The HIV protease (also called proteinase)
processes viral core and polymerase proteins to make infectious virions. When it is blocked
by specific inhibitors, noninfectious viral particles are produced. The glycosidase inhibitors,
through their blockage of glycosylation pathways, prevent glycoproteins formation in the
late stage of HIV life cycle. These agents have been shown to be effective in vitro. Finally,
gene therapy, vaccine therapy and cytokine therapy (with, say, interleukin-2) are also
potential candidates for treating HIV infection.

102
Combination therapy

Because of the intrinsic problems of

Goals drug failure, viral resistance and drug
* more potent inhibition of viral toxicity in treating HIV infection with single
replication agents, combination therapy was
* delay emergence of drug-resistant increasingly being tested. This approach is
virus not new from the past experience of treating
* reduce drug toxicity and thus other infections like TB or cancer. It has the
better tolerance potential advantages of achieving a
synergistic or additive effect on reducing
viral burden, slowing development of drug
resistance, and decreasing drug toxicity if a
lower dose of each agent is used or they are
used in alternation. Moreover, combination
treatment may effectively target different cell
types or tissues infected by the virus. It is
important, however, to be sure that the
interaction of drugs employed for
combination should not result in
antagonism.

The agents used for combination may

act at the same target site (convergent
combination) or different sites of the HIV life
Approaches
cycle (divergent combination). The drugs
* convergent vs divergent
may be administered at the same time
* simultaneous vs alternating
(simultaneous) or one after the other
(alternating). The simultaneous approach
may be more efficacious whereas the
alternating approach may ameliorate certain
drug toxicity by allowing a washout period
for an intolerant drug, and thus may be best
suited for patients with advanced disease. In
fact, the combination of zidovudine and
zalcitabine or didanosine has been
investigated in several preliminary studies
and the initial results were promising.
Combination of two to three nucleoside
reverse transcriptase inhibitors and non-
nucleoside analogues or agents that act at
other target sites are also tested.

103
Current strategy and future direction

Though still a relatively new area,

Current recommendation some guidelines can be drawn up regarding
* zidovudine as first line drug the use of antiretroviral agents. Zidovudine
* switch to or add didanosine or is the first-line drug for patients with
zalcitabine if zidovudine fails advanced or symptomatic HIV disease or
or cannot be tolerated when CD4 count falls below 200/ul. Its use
* may consider early combination may also be considered for asymptomatic
therapy for motivated patients patients with CD4 count less than 500/ul,
who do not have prolonged particularly when there is evidence of
zidovudine increasing p24 antigenaemia or rapidly
declining CD4 level. Usually 500 to 600mg in
three divided doses is administered every
day, and in case of poor tolerance to the
recommended dose, a lower daily dosage is
indicated but should be no less than 300mg.

If there is zidovudine intolerance or failure, either didanosine (125 or 200mg twice daily)
or zalcitabine (0.75mg thrice daily) monotherapy is indicated. Alternatively, combination
therapy by adding didanosine or zalcitabine to zidovudine can be tried when disease
progression occurs in patients tolerating zidovudine. Stavudine can be considered if
patients fail or are intolerant of the other antivirals. In arriving at any of the treatment
decisons, the patient should be adequately counselled and encouraged to make the most
appropriate choice.

__________________________ While the current generation of

_ nucleoside reverse transcriptase inhibitors
has not dramatically improved the survival
The way ahead of AIDS patients, they certainly have
* documentation of better prolonged the symptom-free period and
combination regimen delayed the onset of AIDS. This means a
* development of other more potent better quality of life for the majority of
antivirals patients. It seems very likely that in future
* overcoming the problems of drug combination therapy is the way to go by.
interaction and toxicity ‘A ggressive’ institution of drugs in
* ?sequential use of several drugs combination starting at an early stage of HIV
at a time to minimise residual infection may result in better drug tolerance,
viral replication delay emergence of drug resistance, achieve
* ?aggressive antiviral therapy at potent inhibition of viral replication and
time of seroconversion if detected hopefully, result in slower disease
progression and eventually better survival.
It is possible that combination therapy may
be used as the first line treatment or within a
few months of monotherapy.

104
 Several questions, however, remain to be answered - (i) which combinations of drugs
are least toxic while most durably efficacious, (ii) will combination delay or limit the
emergence of multiple resistant strains and (iii) how important is the mode of drug
administration e.g. simultaneous, alternating, intermittent or sequential. Different agents that
are active against both acute infection of new cells and HIV replication in infected cells
should probably be encouraged in the combination approach. The chronic nature of HIV
infection underscores the need for prolonged therapy. In this regard, new, safe and more
effective drugs have to be continually developed. Finally, the patient should always be
involved in making decision regarding his/her antiretroviral therapy, at present and also in
the future. Clear information shall be given, alternatives thoroughly discussed and support
rendered to backup their informed decisions.

Recommended dosages, monitoring and common side effects of registered

antiretrovirals in Hong Kong

Drug Dosage Monitoring Common side effects

ZDV 500-600mg/D in three divided CBP every 2 weeks for anaemia,

doses (adult) 2 months, then every neutropaenia,
180mg/m2 q6H, ceiling dose of 4 weeks gastrointestinal upset,
1000mg/D suggested (children) LFT,CPK every 4 CNS symptoms,
weeks myalgia

DdI (adult) >60kg: 200mg BD CBP, RFT, LFT, uric pancreatitis,

<60kg: 125mg BD acid, amylase, CPK, peripheral
(children) 90-135mg/m2 B D ankle jerks, sensation neuropathy,
every 4 weeks diarrhoea

DdC 0.75mg TDS (adult) CBP, LFT, amylase, peripheral

0.01mg/kg q8H (children) uric acid, CPK, ankle neuropathy,
jerks, sensation every pancreatitis, rash,
4 weeks mouth ulcers

105
 6. PRIMARY CARE & PSYCHOSOCIAL SUPPORT
OF HIV/AIDS

6.1 HIV/AIDS counselling and support

Counselling is an indispensable
component of a succcessful intervention
Aims of HIV/AIDS counselling and care programme for people with
1. provide psychosocial support HIV/AIDS. The reasons are: there is as yet
2. prevent spread of infection no cure for the disease but prevention of
further spread is feasible; the infection
carries with it at least as many social
meanings as the physical ones, if not more.
The psychosocial consequences can in fact
cause more sufferings for HIV-positive
people than the medical complications.
HIV/AIDS counselling aims at (1) providing
psychosocial support for people infected
and affected by the disease and (2)
preventing further HIV transmission. These
obviously cannot be achieved without a
trusting relationship between the client and
the care-provider or counsellor, a tailored
and personally relevant health education
and behavioural change programme, and a
comprehensive support system.

Pre-test counselling

In light of the possible medical, social, emotional, financial, insurance and personal
implications of being identified HIV positive, pre-test counselling should be offered to all
subjects undergoing voluntary antibody testing. HIV test should never be regarded as a
routine medical test. Explicit informed consent shall be obtained. The meaning and
limitations of the HIV test, interpretations of positive or negative results, actual testing
process and issues of confidentiality and notification (not a notifiable disease) should be
explained. For example, it should be emphasised that the test only detects past exposure to
and infection by the virus but not AIDS, and that false negative result may arise during the
window period. The risk of acquiring HIV has to be assessed, both in contexts of sexual and
drug taking behaviours and the possible occupation-related aspects for health care workers.
Preventive education tailored to the individual situation is necessary.

P o t e n t i a l c o n s e q u e n c e s o f a p o s i t i v e r e s u l t s h a l l b e d i s cu s s e d t h o r o u g h l y . T h e y a r e :
the natural course of HIV/AIDS; psychological impacts to the infected person, his partner,
family and friends; accessibility of medical serivces; local insurance policy; social
stigmatisation and discrimination; and possible restrictions in employment. The client
should be prepared that the result may indeed be positive. The social responsibility of HIV

106
positive people in preventing further spread of infection should be explained. In contrast to
the negative impact being identified positive, the benefits of early diagnosis and
management should also be given. An HIV-infected person is also better able to plan his
future when he is certain of the diagnosis. Pre-test counselling also provides the
opportunity to clear misconception, relieves distresses which may arise from HIV/AIDS, and
assess the possible reaction and coping strategy with a positive diagnosis.

Post-test counselling of negative result

At this juncture, the counsellor shall

make assessment on whether the client had
* clear explanation of the meaning of had any high risk behaviours during the
a negative result intercurrent period. Despite a negative
* reassessment of risk behaviours result, preventive information and the
* reinforcement of changes for safer importance of sustained refrainment from
behaviours risky AIDS-related behaviours has to be
readdressed. Techniques of safer sex
practice and harm reduction in drug-taking
behaviours shall be covered. Assessment of
their understanding and acceptance should
also be made to ensure better compliance.
Some worried well with a negative status but
continued anxiety may need reassurance
and possibly referral to a specialist
psychologist.

Counselling of people with positive result

The positive HIV result should be

Key points in initial counselling clearly and directly conveyed to the
Of positive people patients. For some, the immediate reaction is
* reassure confidentiality usually that of shock, denial, anxiety and
* safe and supportive environment depression. Some feel as if they are given a
* enough time for emotional airing death sentence. Emotional ventilation is
* discuss who and what to tell prudent, as is reassurance of strict
* importance of follow-up confidentiality of HIV status. Issues like
* assess existing support and its who to inform, what needs to be said, and
adequacy importance of follow-up ought to be
* provide lifeline for crisis discussed. Sufficient time should be allowed
intervention for patients to talk and express their feelings
* infection control and avoid spread and concerns. A counsellor's (or a care
of HIV (may require practical help) provider's) support is crucial and the release
of result should not be made lightly, e.g.
over the phone. Misconceptions should be
cleared. Psychological and practical support
is to be offered, including crisis intervention,
besides identifying their own support
channels.

107
 It is unlikely that a patient can take in much information at this news-breaking stage.
Another appointment later, after stabilisation of the patient's emotion, is necessary to
discuss things in more detail and to plan ahead the future management. Some of the issues
to be covered include health implications, access to psychosocial support services, rights
and responsibilities, confidentiality, household infection control measures and safe
practices regarding sex and drug use. The involvement of partner or the closest person is
ususally important and useful.

Follow-up psychosocial support

After overcoming the first crisis in

Provision of ongoing support knowing the positive HIV result, the patient
* address issues like relationship, may have to face multiple crises in the
health maintenance, coping course of the disease. On-going counselling
difficulties and social problems support, monitoring of psychological well-
* regular review of protective being, and attention to personal and social
behaviours and areas of concern problems are as essential as attending to
* support rendered in various forms one's physical health. Early establishment of
e.g. individual counselling, peer suitable coping and support mechanisms
support group, buddy system, can be advantageous in anticipation of crisis
practical daily living aid, other which may arise in the future. Progression of
community resources the disease, with, for example, a falling CD4
count, appearance of new complications,
need for antiviral therapy or even
development of AIDS, may lead to
psychological trauma. Particular attention
has to be paid for its psychosocial
consequences when the disease advances,
and appropriate interventions should be
undertaken.

Various forms of counselling and psychotherapy may be needed in the continuing care
of the patients, to address issues like loss of self-control, social discrimination, family
relationships, friendships, sexuality, changes in lifestyle, grief, bereavement and death. Self-
help support group for sharing of experience and mutual support can be an important outlet
for some individuals. In some cases, the operation of support groups can be facilitated by a
counsellor. Buddy system provides companionship and help from a volunteer who
functions as a friend. Practical support for activities of daily living, e.g. cooking, clothes
washing, house cleaning and shopping, may require other forms of community
mobilisations, e.g. support of home-help service. Other social issues, such as financial
hardship, employment and housing also need to be addressed. Of course, the patients'
spouse/partner, other family members or close friends may become the principal carers. In
turn, support for them is necesary as they may be faced with enormous stress in the process
of providing care, especially when the patient is progressing to late stage of the infection.

109
 6.2 Confidentiality

Preserving confidentiality of patients ’

Rationale of protecting conditions and medical records has always
Confidentiality for HIV/AIDS been the cornerstone of good medical
* protect patients from social stigma practice, even before the AIDS era. Given
and discrimination attached to the the immense psychosocial and legal
disease implications of HIV/AIDS, strict
* Public health interest by gaining confidentiality is crucial for a successful
trust and co-operation of infected management programme. Maintaining
and at risk people confidentiality is actually the key
requirement for encouraging at risk people
to seek HIV testing, counselling, support
and care. It is thus a critical component of
public health strategies for the control of the
disease.

In Hong Kong, the government and the medical profession have adopted ethical codes
of practice and policies enforcing strict compliance with the rule of confidentiality. Such
codes are considered reasonable standard of care, the negligence of which may be treated as
evidence resulting in legal claims. Consent should always be sought from the patient before
conveying medical information (including one’ s HIV status) to other people, including other
health care professionals.

There are certain grey areas in the maintenance of confidentiality. One example is that
when a patient knowingly continues to place others at risk of HIV infection through the
practice of high risk behaviours. If the person at risk is identified, and especially when
he/she is also a patient of the same doctor, the latter may have a duty to warn of the risk.
Health care workers are required to act reasonably to counsel the patient about possible risk
of infection and also minimising the risk of transmission.

110
 6.3 Primary care of HIV/AIDS

In spite of the short history of HIV/AIDS in medicine, it has generated so much

debates, questions and controversies within the health care and the wider community that
no disease has ever had. From the very start of the epidemic when clinicians knew that there
was a new mysterious disease affecting human beings, through the evolution of care for
HIV-infected patients and to the development and change of the epidemic, there are many
lessons that health care professionals, scientists, policy makers and the society can learn.

Professional responsibility to care

T h e h e a lt h c a r e p r o f e s s i o n h a s n e v e r
been an absolutely ‘ s afe ’ working
Health care profession environment throughout its history. Health
* inherent known and unknown risk care workers have been, are and will
of the work continue to be exposed to risk of acquiring
* professional obligation to provide different diseases and injuries, while they
quality care to all patients are delivering or contributing care to
patients. As long as they are pursuing with
this mission, they should understand that
the risk can be minimised by good strategy,
but never to zero. It is, however, the ethical
obligation of health care professionals to
provide the best possible care to all patients,
irrespective of factors like race, sex, and also
disease of the patients, just to name a few.
Refusal to care for patients on the ground of
unaccepatable personal risk or dislike
towards certain people is morally and
professionally inappropriate.

Sadly enough, even in the second decade of the HIV/AIDS epidemic, we are still
seeing HIV positive patients being denied of care and treatment by health care workers.
Perceived risk of being infected while providing care for patients with HIV is definitely a
concern for some people. The reluctance of some workers may be further explained by their
judgemental attitude towards the disease and also the patients, as the infection is thought to
b e a s s o c i a t e d w i t h ‘ im m o r a l’ b e h a v i o u r s . T h e p u b l i c w i l l n a t u r a l l y n o t b e c o n v i n c e d a b o u t
the low risk of transmission of HIV in health care setting if the workers themselves refuse to
care for patients infected with HIV. Personal values leading to inacceptance of things such
as homosexuality and substance abuse are difficult to tackle. It is important, therefore, to
provide education starting early in the professional training. Health care workers should also
try to counsel those colleagues who are uncomfortable in providing care to HIV-infected
people.

Nursing care

111
 Caring for HIV-infected patient s i s a
very challenging but rewarding task. The
Care of HIV-infected patients variable course of the infection from
* demonstrates the importance of progression of asymptomatic disease to
holistic and multidisciplinary bouts of life-threatening illnesses, highly
approach complex psychosocial factors entangled
* stimulates new and better models with the disease and the lack of a cure at
of care to serve as reference for present have all contributed to the
other patients difficulties and dilemma when providing
HIV/AIDS care. The nursing experiences
gained in responding to the needs of
patients with HIV have shed light to the
development of alternative and innovative
models of nursing care for patients in
general. A holistic approach with attention
to physical, psychosocial and spiritual
needs of patients is the goal to work at, and
patients should be actively involved as
appropriate in their own care. Nurses can
also play a role in the preventive education
of and advocacy for HIV/AIDS within their
profession and the society.

The basic nursing skills for direct care of patients with HIV infection is no different
from those for patients suffering from other diseases. During hospitalisation, there is no
need for routine isolation of HIV-infected patients. However, they may require single room
for the following conditions:
• Bleeding
• Great chance to bleed
• Profuse diarrhoea
• Incontinence
• Disturbed level of consciousness
• Unco-operative patients
• Post-operation with open or draining wound
• Poor patient hygiene with contamination of environment by blood, secretion or
excretion
• Suffering from an opportunistic infection that is contagious e.g TB

112
Role of primary care physicians

The association of HIV transmission

with certain risk behaviours that are greatly
* preventive education for patient influenced by social factors has contributed
* peer education among colleagues to its spread. Some at-risk or HIV positive
* diagnosis and treatment of STDs people would seek appropriate advice and
* diagnosis of HIV treatment. Some are, however, unrealised of
* counselling their risk or evade the issue. The nature and
* care and treatment potential magnitude of HIV infection among
targeted or general populations demands an
input from primary care physicians, in
providing services that range from (1)
offering HIV antibody screening to at risk
people; (2) assistance in the local
surveillance programme; (3) health
education; and (4) management of HIV-
infected individuals. Primary care physicians
have been long valued for their role in
providing basic medical care and advice for
their patients. Their forefront contact and
established relationship with patients have
facilitated handling of such issues as risk
assessment, and prompting disease
prevention through behavioural
modifications.

Diagnosis of HIV infection requires a screening test and confirmatory test. Since 1989,
the Virus Unit of the Department of Health has been providing free confirmatory tests to
other laboratories with positive screening results. A high index of clinical suspicion is
needed for diagnosing HIV/AIDS, which can be confirmed with laboratory investigations.
The HIV testing has, however, to be done with pre-test counselling (section 6.1).

In the past decade, HIV/AIDS has evolved from a hospital-based medical specialty to a
subject of primary care concern. Except for those with late and fulminant diseases, HIV
positive patients can often be managed on an outpatient basis. Advice on a healthy life
style e.g. adequate nutrition, rest and exercise, is important. They should also be
encouraged to refrain from risk behaviours that can both activate their infection and pass on
the virus to others. Regular follow-up and monitoring of one's health is essential. Attention
to emotional and social aspects of the disease, with appropriate intervention and support,
should also be paid. Early collaboration with services of the specialist clinic will be
beneficial. It is crucial that primary care physicians are involved in the fight against spread
of HIV/AIDS and care of people infected and affected by the disease. In order to achieve
this, they have to have broadened awareness of the disease, as well as knowledge about its
common problems and management.

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 7 . H I V T R AN S M I S S I O N I N H E A L T H C A R E S E T T I N G

7.1 Introduction

Occupationally-acquired HIV infection among health care workers is an insignificant

factor in contributing to the overall HIV problem globally. The risk of being infected after
occupational exposure to HIV-contaminated body substances has also been documented to
be extremely small. The average risk is less than 0.4% with percutaneous injury by an HIV-
contaminated needle. Yet, the social implications of HIV/AIDS have led to apprehension and
disproportionate fear among health care workers who have been or are likely to be exposed
to HIV during their work. It is universally accepted that stringent adherence to standard
infection control practice is essential for preventing HIV and other transmissible diseases in
the health care setting.

The issue of patients infected by HIV while receiving treatment in health care setting
has raised much public concern. This was fuelled after the report in 1992 of five patients who
were infected with the virus after undergoing dental procedures in the clinic of a dentist in
Florida, USA. The strong public response to an isolated rare event has, once and again,
reminded us that HIV infection carries with it much more social meanings than medical
implications. Other investigations undertaken in USA, UK and Australia in the recent few
years on patients of several HIV-infected surgeons, obstetricians and gynaecologists have
not identified any transmission. These patients have all undergone operations or other
invasive procedures by their doctors, before the positive HIV status of the doctors was
revealed.

In 1993, another incident of patients being infected in health care setting was reported
in Australia. This time HIV transmission has probably occurred from patient to patient: an
HIV-infected patient had passed the virus to four patients who underwent minor surgical
treatments in a private clinic in Sydney. The report has not received wide media attention in
Hong Kong. There was recently another report of possible nosocomial transmission of HIV
to an infant, and transmission to patients in a dialysis centre.

To date, these few reports represented the only known incidences of HIV transmission
from health care workers or patients to other patients. After thorough investigation of the
case of Florida dentist by a committee, it can only conclude that the most likely route of
transmission was from the infected dentist to the patients, but the exact mechanism was still
unknown. The Sydney case has probably resulted from patient-to-patient transmission,
possibly due to breakdown of infection control at some point of the surgery. The risk of HIV
transmission to patient in health care setting has been difficult to be calculated, as it is a
heterogenous situation affected by many variables and confounding factors. Yet, the risk is
likely to be much lower than that of transmission to health care workers from HIV-infected
patients. Nevertheless, these instances further demonstrated the importance of ensuring

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quality infection control practices and procedures in preventing communicable diseases, in
particular blood-borne ones, in health care establishments.

7.2 Recommended guidelines and practices

relating to prevention of transmission
of HIV in health care settings

The prevalence of HIV infection appears to be low in Hong Kong (<0.1%). Because it is
often impossible to know when an individual has been infected with HIV or other blood-
borne pathogens, and in light of the high prevalence of hepatitis B virus infection in the
community, guidelines and practices that reduce health care workers ’ exposure to blood and
b o d y f l u i d s o f all p a t i e n t s s h o u l d b e d e v e l o p e d . A p p r o p r i a t e w o r k p r a c t i c e s , i n c l u d i n g
protective barriers to prevent parenteral, mucous membrane and non-intact skin exposure to
blood and certain body fluids (amniotic fluid, pericardial fluid, pleural fluid, peritoneal fluid,
synovial fluid, cerebrospinal fluid, semen and vaginal secretion) of all patients, should be
adopted. The risk of HIV transmission from faeces, nasal secretion, sputum, sweat, tears,
urine and vomitus without overt blood staining is extremely low or non-existent. As all
available evidence indicates that percutaneous injury with sharps is the most common mode
of blood-borne pathogen transmission in health care settings, all sharps and potential
sharps should be handled with extreme care.

Health care workers who consider themselves at increased risk of HIV infection should
arrange confidential testing. Those who are infected must seek appropriate medical advice
to ensure they pose no risk to patients.

When performing invasive procedures, higher risk of blood-borne pathogens

transmission is expected. Health care workers must be protected from mucocutaneous
e x p o s u r e t o t h e p a t i e n t’ s b l o o d a n d t h e p a t i e n t m u s t b e p r o t e c t e d f r o m i n t r a o p e r a t i v e
wound contamination. The use of special precautionary measures based on the nature of
surgical procedures is justifiable .

The following recommendations outline work practices and barrier techniques that
should be adopted in in-patient and out-patient settings, including Accident and Emergency
Department and ambulatory care settings. The recommendations are based on current
available information. Infection Control Committees of all health care institutions are urged
to familiarise themselves with these recommendations and adapt them in light of local
circumstances and requirements. The adopted precautions should then be widely
disseminated to all health care workers.

Precautions for General Care

(a) Protective Barriers

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 (i) Gloves

Gloves should be worn for direct contact with blood and body fluids, as well as
contact with mucous membrane and non-intact skin of all patients. They should also be
worn when handling contaminated items or surfaces.

When performing phlebotomy procedures, there may be a possibility of contamination

with blood. If there is a likelihood of hand contamination with blood, the wearing of gloves
is advisable.

If gloves are worn, they should be changed after contact with each patient and before
administering care to another patient, whenever torn and when a needle-stick or other injury
occurs.

General purpose utility gloves such as rubber household gloves may be used for
housekeeping chores involving potential blood contact, as well as for instrument cleaning
and decontamination procedures. Utility gloves should be decontaminated and reused if
still in satisfactory condition.

(ii) Masks and Protective Eyewear

Masks and protective eyewear or face shields should be worn when the splashing of
blood and body fluids is anticipated.

(iii) G o w n s a n d A p r o n s

Gowns or aprons should be worn during procedures that are likely to cause the
spattering or splashing of blood and body fluids.

(b) Hands

All skin defects should b e covered with waterproof dressing.

Hands must be washed after examining patients or touching potentially contaminated

articles and before taking care of another patient.

Hands and other skin surfaces should be washed with soap and water immediately and
thoroughly if contaminated with blood or other body fluids.

(c) Rooms

A single room may be indicated for a patient with profuse bleeding that is likely to
cause environmental contamination, or when patient hygiene is poor, for example, when a
patient contaminates the environment with blood, secretion or excretion.

Individuals with known HIV infection often suffer from other infectious diseases, such
as tuberculosis. They should be placed on isolation precautions as recommended by the
Infection Control Committee of individual hospital.
(d) Sharps

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 Precaution should be taken to prevent injuries caused by needles, scalpels and other
sharp instruments or devices during procedures, when cleaning instruments, during
disposal of used needles and handling sharp instruments after procedures.

USED NEEDLES SHOULD NOT BE RECAPPED. If recapping of needles is necessary,

a ‘s coop’ technique or a needle recapping device should be used.

All used sharps should be placed in a puncture-resistant sharps box which should be
located in the area where it is used. Do not overfill the sharps box.

Used sharps box should be placed in red plastic bag and disposed of as medical waste.

(e) Specimens

All patients ’ specimens should be placed in sturdy leak-proof containers with secure
lids to prevent leaking during transport. Care should be taken when collecting and handling
specimens to avoid contamination of the outside of the containers and the laboratory
request slips accompanying the specimens. When the primary container is subject to
leakage, or the specimen is to be transported between institutions, a secondary leakproof
container such as a zip lock clear plastic bag should be used. Request slips should be
placed outside of the secondary container.

(f) Accidental Exposure to Blood or Body Fluids

In case of penetrating injury or mucocutaneous exposure to blood and body fluids, the
injured or exposed areas should be washed with copious amount of running water. Minor
penetrating injury should be encouraged to bleed.

All incidents of exposure to blood or body fluids, either parenteral or mucous

membrane exposures, should be reported. Appropriate serologic testing, medical evaluation
and follow-up should be performed in accordance with institutional policy for hepatitis B.
Advice could be sought from the AIDS Unit of the Department of Health, the individual
hospital's Infection Control Unit, Staff Clinic or Accident & Emergency Department.

(g) Decontamination of Articles and Environment

All equipment to be used should be disinfected in accordance with hospital

disinfectant policy.

H I V i s s e n s i t i v e t o h e a t . S t u d i e s s h o w e d t h a t i t i s i n a c t i v a t e d b y m o i s t h e a t a t 6 0 oC in
30 minutes. It is also inactivated rapidly after exposure to commonly used chemical
disinfectants at concentration much lower than those used in routine hospital practice.
Depending on the amount of blood and mucus present on the surface to be cleaned and
disinfected, a solution of sodium hypochlorite (household bleach) in concentration ranging
from 1,000 ppm (1:50 dilution) to 10,000 ppm (1:5 dilution) available chlorine is effective.

Thorough cleansing before disinfection or sterilisation is an important part of all

decontamination procedures. Heating is the most effective method of disinfection. For heat

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sensitive items, immersion in 1,000 ppm hypochlorite solution for at least 10 minutes should
be effective. For metal devices which might be corroded by repeated exposure to
hypochlorite solution, 2% glutaraldehyde for 10 minutes is recommended.

Spills of blood and body fluids should be cleaned up as soon as possible. They
should be removed with disposable absorbent material held in a gloved hand. The spill site
should then be wiped down with paper towel soaked in 10,000 ppm hypochlorite solution.
This should be rinsed off to reduce the risk of surface damage, particularly if used on metal
surface.

No special precautions are necessary for dishes, drinking glasses and eating utensils.
Individuals with known or suspected HIV infections should have their meals served with
ordinary eating utensils. These can be cleaned together with those used by other patients
in accordance with the institutional policy. There is no need to use disposable items.

Environmental surfaces such as wall, floor and other surfaces have not been
associated with the transmission of HIV. Common housekeeping procedures are adequate
for cleaning environmental surface.

(h) Laundry

All used linen should be bagged at the location where it is used. Linen should not be
sorted or rinsed in patient care areas. There is no need to use disposable linen for HIV-
infected patients.

Linen soiled with blood or body fluids should be disinfected with 1,000 ppm
hypochlorite solution for 30 minutes and then bagged and sent to the laundry.
Alternatively, untreated soiled linen can be placed in alginated bags for treatment in the
laundry.

Linen should be washed with detergent in hot water. The temperature of the items in
the machine should be maintained at over 800 C for at least 10 minutes.

(i) Waste Disposal

Waste should be disposed of in accordance with the established institutional policy.

Medical wastes should be discarded into red plastic bags with minimal handling. They
should be sent for incineration or stored in a designated location to be collected by
USD/RSD staff.

Blood, excretion and secretion may be carefully poured down a drain connected to the
sewer system.
Precautions for Invasive Procedures

Invasive procedures are those diagnostic or therapeutic procedure s that involve

surgical entry into tissues, body cavities or organs, or repair of major traumatic injuries. As
it is recognised that the risk of accidental exposure to blood and body fluids during these
procedures cannot be reduced to zero under current technology, depending on the types of
operation, the length of operation, blood loss and the requirement of irrigation, special

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precautionary measures may be required. In general, when performing “ exposure-prone”
procedures, or procedures which are predicted to last longer than 3 hours, and result in
blood loss greater than 300 ml, in addition to the procedures adopted routinely to prevent
cross-infection, the following barrier protection should be used :

(a) The surgical team should wear two pairs of gloves.

(b) Protective eyewear should be worn to avoid conjunctival contamination.
(c) A disposable plastic apron should be worn by the scrubbed team under their gowns
and by other staff in the theatre.

Precautions for Dialysis

(a) Patients with suspected or known HIV infection who require haemodialysis or
peritoneal dialysis can be dialysed in any hospital based or free standing dialysing
unit that uses standard infection control precautions. A single room is preferable for
HIV infected patient undergoing haemodialysis.
(b) Haemodialysis machines should be disinfected with 500 - 750 ppm hypochlorite
solution for 30-40 min. or 4% formalin overnight.

Precautions for Endoscopy

(a) All endoscopists must wear gloves, gown, mask and protective eyewear.

(b) All p r o c e d u r e s s h o u l d b e p e r f o r m e d i n r o o m s w i t h a d e q u a t e v e n t i l a t i o n . For

bronchoscopy, as far as practicable, the rooms should have negative pressure with >6
air changes per hour.

(c) Use totally immersible endoscopes as far as possible.

(d) The endoscope should be cleaned and disinfected at the beginning of the first
procedure of the day and after each procedure.

(e) In between cases, after thorough cleaning which should include irrigating and
brushing of channels, the endoscope and all internal channels should be soaked in 2%
glutaraldehyde for at least 5 min. (at least 30 min. for bronchoscopy).

(f) After the glutaraldehyde soak, the channels should be rinsed with sterile water
followed by wiping the insertion tube with 70% alcohol.
(g) Use autoclavable biopsy forceps and cytology brushes. A separate pair of biopsy
forceps and cytology brush should be used for each patients. Do not use a needle to
remove biopsy materials from biopsy forceps.

Precautions for Dental Surgery

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 Blood, blood contaminated saliva and gingival fluids from all patients should be
considered infective and appropriate barriers should be used during dental procedures in all
health care settings. Procedures adopted routinely for all practices must be adequate to
prevent cross-infection.

Please refer to documents on prevention of cross infections in dental settings

promulgated by the Hong Kong Dental Association or the Department of Health.

Precautions in Clinical Laboratories

• Blood, serum, unfixed tissue and tissue fluids from all patients should be considered
potentially infective. Minimal risk of HIV transmission is presented by urine, saliva
and faeces without overt blood staining, though they may contain other pathogens.
• Laboratory access should be restricted to authorised staff only.
• Eating, drinking, smoking and the application of cosmetics should be prohibited in the
laboratory.
• Labora tory coats, gloves or other protective clothing should be worn to prevent
contamination of exposed skin and soiling of clothing. Protective clothing should be
changed if visibly contaminated with blood or body fluids, and should always be
removed before leaving the laboratory.
• Care should be taken when opening specimen containers to prevent splashing or
spattering. Routine procedures with blood and body fluids can be performed on an
open bench. However, processing of specimens which are likely to create splash
should be carried out with gloved hands in a biological safety cabinet. Alternatively,
laboratory personnel should wear protective barriers including gloves, masks,
protective eyewear to prevent the contamination of skin or mucous membrane.
• Centrifuges with sealed buckets, safety cups or sealed heads should be used to
prevent the escape of liquids or aerosols.
• M e c h a n i c a l p i p e t t i n g d e v i c e s m u s t b e u s ed f o r t h e m a n i p u l a t i o n o f a l l l i q u i d s i n t h e
laboratory. Mouth pipetting must not be allowed.
• Laboratory and quality control reagents containing or derived from blood or blood
products should be considered potentially contaminated.
• Needles and syringes should be used only when necessary and in a situation in
which there is no alternative. The use of plastic pipettes should be encouraged. Care
should be taken to prevent injuries caused by needles, scalpels, glass slides and other
sharp or breakable instruments or devices. Needles should not be recapped or
manipulated by hand. Disposable needles and other sharp items should be placed in
a puncture-resistant sharps box for disposal after use. These containers should be
located as close as practical to areas where they will be used.
• Laboratory work surfaces should be decontaminated with 1,000 ppm hypochlorite
solution on a daily basis and following spillage of blood or body fluids. For large
spills of cultured or concentrated infectious agents, the contaminated area should be
first flooded with 10,000 ppm hypochlorite solution before cleaning, and then wiped
down with disposable towels in a gloved hand.
• Automated machines should have designs to avoid splashing or be adequately
screened. There should be a closed system from specimen presentation to safe
discharge of effluent, and should accept periodic disinfection readily.

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• As far as possible, equipment should be decontaminated before they are sent for
mechanical or electrical servicing.
• Tissue or serum specimens to be stored should be clearly and permanently labelled as
potentially hazardous.
• Infective waste from the laboratory should be autoclaved before disposal or sent for
incineration.

Precautions for Handling and Disposal of Dead Bodies

Although most organisms in the dead body are unlikely to infect healthy persons,
some infectious agents may be transmitted where workers are in close contact with blood,
body fluids and tissues of dead body who died with infectious diseases. To minimise the
risks of transmission of known and also unsuspected infectious diseases, dead bodies
should be handled in such a way that workers' exposure to blood, body fluids and tissues is
reduced. A rational approach should include staff training and education, safe working
environment, appropriate work practices, the use of recommended safety devices and
vaccination against hepatitis B.

There is a need to maintain the confidentiality of patient's medical condition even after
the death of the patient, particularly when stigmatising conditions, like human
immunodeficiency virus (HIV) infections, are involved. At the same time, there is obligation
to inform personnel who may be at risk of infection through contact with deceased person to
take appropriate measures to guard against infection. The discrete use of labelling such as
‘ Danger of Infection’ on the dead body is considered appropriate.

The following outline work practices which are recommended when handling and
disposing dead bodies. These have been formulated by a working party comprising
representatives of the Department of Health, Hospital Authority, Urban Services Department
and Regional Services Department. Hospitals, public mortuaries and funeral parlours are
urged to adapt them in light of local circumstances and requirements. The adopted
precautions should be widely disseminated to all staff involved.

Recommended procedures at the workplace

I Last office for the dead body by ward staff

I.1 For all dead bodies other than those with infectious diseases as listed in Appendix
VIII

1. Nursing and other personnel who handle dead bodies must wear protective clothing
consisting of gown/apron and gloves. They should cover all cuts and abrasions with
waterproof bandages or dressings.
2. Wound, drainage and needle puncture holes should be disinfected with 1% household
bleach (1:5 dilution and must be freshly prepared) and dressed with non-permeable
material.
3. Extreme caution should be exercised when removing intravenous catheters and other
devices which are sharp. They should be disposed into puncture resistant containers.

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4. All body orifices should be plugged with swabs soaked in 1% household bleach (1:5
dilution).
5. The body should be cleaned and dried.
6. A f t e r i d e n t i f y i n g a n d a t t a c h i n g t o t h e b o d y t h e n e c e s s a r y i d e n t i t y l a b e l s , th e b o d y
should be wrapped with mortuary sheet before being placed on mortuary trolley and
transported to the mortuary.
7. After removing protective clothing and gloves, hands should be washed thoroughly.

I.2 Precautions for handling dead body with infectious disease as listed in Appendix VIII

1. To obviate the need for the undertaker to handle the body, following I.1.1 - I.1.5, it is
preferable for the ward staff to dress the deceased. The relatives should be informed
beforehand so that they can bring the necessary clothing in advance.
2. Identify the body and attach to the body the necessary identity labels. The body
should be placed in a robust, transparent plastic bag made of polyethylene of not less
t h a n 1 5 0 µm t h i c k . The open end of which should be closed tightly with tapes and
bandage strips. Pins are not to be used.
3. The outside of the plastic bag should be wiped with 0.1% household bleach (1:50
dilution).
4. The bagged body should be wrapped with mortuary sheet before being placed on
mortuary trolley and transported to the mortuary.
5. Warning labels such as `Danger of Infection' should be attached to body/body bag,
mortuary sheet and accompanying paperwork.
6. D i s p o s a b l e i t e m s s h o u l d b e d i s c a r d e d i n t o r e d p l a s t i c w a s t e ba g w h i c h s h o u l d b e
securely tied up and sent for incineration.
7. Used linen or protective clothing should be autoclaved or soaked in 0.1% household
bleach (1:50 dilution) for 30 mins.
8. E q u i p m e n t s h o u l d b e a u t o c l a v e d o r d e c o n t a m i n a t e d w i t h d i s i n f e c t a n t so l u t i o n s i n
accordance with established disinfectant policy.
9. All surfaces which may be contaminated should be disinfected with 0.1% household
bleach (1:50 dilution) or 1% printol.
10. A f t e r r e m o v i n g p r o t e c t i v e c l o t h i n g a n d g l o v e s , h a n d s s h o u l d b e w a s h e d t h o r o u g h l y .
11. The mortuary staff-in-charge should be informed that there is potential risk of infection
if there is possibility of contact with blood, body fluids or tissues.

II Precautions in mortuary

II.1 General precautions

1. All staff should be trained in the prevention of infections. A high standard of personal
hygiene should be adopted.
2. Smoking, drinking and eating is forbidden in post-mortem room, body storage and
viewing areas.
3. The mortuary must at all times be kept clean and properly ventilated. Lighting must be
adequate. Surfaces and instruments should be made of materials which could be easily
disinfected and maintained.

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4. Staff who handle dead bodies must wear protective clothing consisting of gown, apron,
gloves and boots. They should cover all cuts and abrasions with waterproof bandages
or dressings.
5. All bodies must be identified and correctly labelled.
6. Any dead body which is contaminated with blood or body fluids should be placed in a
disposable plastic bag as soon as possible.
7. B o d i e s s h o u l d b e s t o r e d i n c o l d c h a m b e r s m a i n t a i n e d a t a p p r o x . 4 °C . Storage
compartments should be easily accessible for both regular cleaning and maintenance.
8. Since all bodies who come to autopsy are a potential source of infection, at all times,
pathologists and other support staff should observe universal precautions in the
performance of any autopsy.
9. All efforts should be made to avoid sharps injury, both in the course of examination and
afterwards in dealing with waste disposal and decontamination.
10. Soiled linen, environmental surfaces, instruments and transport trolley should be
decontaminated in accordance with established policy.
11. Single use gloves, protective aprons and other waste materials must be disposed of in
red plastic bags for incineration.
12. A f t e r r e m o v i n g p r o t e c t i v e c l o t h i n g a n d g l o v e s , h a n d s s h o u l d b e w a s h e d t h o r o u g h l y .

II.2 Additional precautions for handling dead body with infectious diseases as listed in
Appendix VIII

1. Autopsies on bodies known or suspected to have died with infectious diseases as

listed in Appendix VIII expose staff to unwarranted risk and should generally not
be performed. However, if autopsy is to be carried out because of special reasons,
the following practices should be adopted :
(i) It should be performed by trained pathologist using recommended barrier
techniques and procedures to reduce the risk of transmission.
(ii) The number of people allowed in the post-mortem room should be limited to
those directly involved in the operation.
(iii) At the completion of examination, after local disinfection of skin with 0.1%
household bleach (1:50 dilution), the body should be placed in a robust plastic
b a g m a d e o f p o l y e t h y l e n e o f n o t l e s s t h a n 1 5 0 µm t h i c k .
(iv) Warning labels such as `Danger of Infection' should be used on the body/body
bag.
(v) The outside of the plastic bag should be wiped with 0.1% household bleach (1:50
dilution).

2. Mortuary staff should ensure that good liaison is maintained between themselves and
those who collect bodies for disposal. It is essential that staff of funeral parlours and all
others involved in handling the body are informed that there is a potential risk of
infection if there is possibility of contact with blood and body fluids.

3. Advice should be given to staff of funeral parlours and relatives regarding the safe
handling of the body (appendix IX).

III Recommended safe working practice for staff of funeral parlours

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1. When handling bodies, do not smoke, eat, drink or take actions that will bring the hands
into contact with mouth, eyes or nose.
2. Make sure that any cuts, wounds or abrasions are covered by waterproof bandages or
dressings.
3. Hepatitis B vaccination is recommended for all staff who are lik ely to come into contact
with dead bodies.
4. Make sure that a supply of disposable gloves, protective clothing and disinfectant such
as household bleach is readily available.
5. Put on disposable gloves and protective clothing/uniform when handling dead b odies.
6. Hands must be washed after removing gloves and protective clothing.
7. Any spilled blood or body fluids must be wiped with 1% household bleach (1:5
dilution).
8. Protective clothing or uniform must be kept apart from outdoor clothing.

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 7.3 Occupational exposure to HIV

Risk and perspective of HIV transmission in health care setting

The risk of acquiring blood-borne

* low but existent risk of infection in the health care settings depends
transmission in health care setting on the nature of the exposure, the size of the
* majority related to HIV- inoculum and the concentration of the
contaminated sharps injury e.g. pathogen in the inoculum. HIV is far less
needle-stick injuries transmissible than hepatitis B virus (HBV)
though both share similar modes of
transmission. The average risk of
contracting HIV after a percutaneous injury
by a contaminated needle is less than 0.4%
whereas it amounts to 6-30% for HBV-
contaminated needlestick injury. As of late
1993, there have been 39 reported HIV
seroconversions among health care workers
in USA that were occupationally-related.
Despite the relatively low risk,
occupationally-acquired HIV infection is
well documented and inoculation with HIV-
infected blood during needle-stick injury is
the principal route associated with infection
occurring in health care setting to date.

The risk of transmission through mucous membrane or non-intact skin exposure

remains too low to be documented, but there have been reports of infection via such
exposure. HIV infection is potentially fatal, and the psychosocial impact related to it is
considerably greater than any of the other known blood-borne diseases. Every precaution
should be taken to further minimise the risk of transmission. The issue of occupational
exposure to HIV infection has to be treated seriously and strategy should be developed
based on scientific data.

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Management of occupational exposure to HIV

Acute management of occupational

* first aid exposure involves the administration of first
* assessment of risk of the exposure aid measures, as soon as patient safety
* see need for hepatitis B permits. The wound, if any, should be
immunisation (passive and active) squeezed lightly to encourage bleeding, and
* counselling for HIV if significant washed with soap and water. The wound
exposure to HIV; check baseline should be disinfected and dressed. Exposed
and follow-up HIV antibody mucous membranes should be
* consider zidovudine prophylaxis decontaminated by flushing with water or
as appropriate saline. The injured person should seek
medical advice for proper wound care and
post-exposure management. Attending
doctors should advise on the need for
hepatitis B prophylaxis and prescribe as
necessary. The injured person may be
referred to the AIDS Unit of the Department
of Health for further counselling and
management.

A mechanism of reporting exposures should be available for every institution and the
information/record should be treated with strictest confidence. For the purpose of
documentation and planning for intervention, assessment should be made regarding the
type, site, mechanism, circumstance, severity, and source of exposure. The source patient
shall, if possible, be evaluated and being offered informed consent to HIV and/or HBV
testing as appropriate.

For significant exposure to proven or potential HIV, the injured person should receive
counselling and baseline HIV antibody testing as soon as possible. Follow-up HIV testing is
usually done at six months after exposure. Exposed persons should be advised to return for
evaluation if symptoms of seroconversion develop. Psychological reactions to the exposure
can be extremely diverse and severe, which may, however, only be evident on careful
questioning and assessment. Clinicians and experts in managing psychosocial stress are
important personnel in tackling these problems, and on-going counselling should be
available. Issues on the protection of third parties, such as sexual partners, and blood/organ
recipient in the event of blood/organ donation, should be discussed and advised.

The administration of chemoprophylaxis with zidovudine remains controversial for

occupational exposure to HIV. The efficacy and long-term safety of the regimen has not
been established, and is hard to be certain in the absence of controlled trial. Animal models
have shown that zidovudine can delay but not eliminate infection after exposure to the virus.
Failure to protect the exposed health care worker has been reported even when prophylaxis
was given. Given the available data, zidovudine treatment should not be taken as the gold
standard for exposed person. The use of zidovudine prophylaxis should be discussed
thoroughly with the exposed person, and shall taken into account such factors as risk

126
assessment, potential side effects of zidovudine and its unproven efficacy. The possibility
of zidovudine resistance in source patients being heavily treated with zidovudine has to be
considered. If the individual person decides to have prophylaxis, it is logical to institute
zidovudine (1000mg daily) as early as possible. It is given for six weeks if tolerable and
acceptable by the person. The person should be monitored for AZT toxicity (while on
prophylaxis) as well as evidence of HIV seroconversion beyond the course of AZT
prophylaxis.

127
 7.4 HIV infection and the health care workers
- recommended guidelines
( formulated by the Advisory Council on AIDS in April 1994 )

1. BACKGROUND

1.1 A I D S ( A c q u i r e d I m m u n o d e f i c i e n c y S y n d r o m e ) i s c a u s e d b y a r e t r o v ir u s n a m e d H I V ,
the human immunodeficiency virus. The syndrome, characterised by development of
complications like opportunistic infections or tumours, was first described in 1981 in the
USA. The human race is now hard hit by the pandemic. An estimated total of 15 million
people worldwide have already been infected so far.

1.2 HIV is transmitted largely through three routes : (a) sexual contact with an HIV-infected
person, (b) exposure to contaminated blood and needles, and (c) perinatally from an infected
mother to her baby. Worldwide over three-quarters of the infection have been contracted
through sex, and largely heterosexual contacts.

1.3 HIV infection has been reported to occur in health care settings by exposure to
contaminated blood through cutaneous injuries or mucous membranes. The estimated risk of
contracting the virus after such injuries or exposure to infected blood is 0.4%.

1.4 The chance of HIV transmission from an infected health care worker to his/her client is
much lower. The CDC ( Centre for Diseases Control ) in Atlanta has reported that six
patients of an HIV positive dentist in Florida were infected since 1990. There is still
controversy as to how the transmission has occurred but this is the only case documented
s o f a r . I n o t h e r ‘ lo o k - b a c k’ s t u d i e s o f o v e r 1 5 0 0 0 c l i e n t s o f 3 2 H I V - i n f e c t e d h e a l t h c a r e
workers, including dentists and surgeons, none was found to have caught the virus.

1.5 Taken the extremely low risk of HIV transmission in the health care setting, universal
precaution in handling blood and other body fluids was generally advocated as the most
effective measure in further minimising the chance of infection. HIV has been isolated from
blood, semen, saliva, tears, urine, vaginal secretion, cerebrospinal fluid, synovial fluid,
breast milk and amniotic fluid of infected individuals. However only blood, blood products,
semen, vaginal secretion and breast milk have been linked to HIV transmission.

2. GENERAL PRINCIPLES

2.1 The most effective means of preventing HIV transmission in health care setting is
through adherence to universal precautions, thereby decreasing the risk of direct exposure
to blood and/or body fluids.

2.2 Voluntary instead of mandatory HIV testing is the best way of encouraging people
(including health care workers) at risk of infection to seek counselling and appropriate
treatment.

128
2.3 Health care workers should consider receiving counselling and HIV antibody testing if
they have reason to suspect that they have been infected.

2.4 Health care workers are generally not required to disclose their HIV status to their
patients or employers. Disclosure, if any, should be made on a need-to-know basis and with
consent of the worker. Maintaining confidentiality is one way to prevent interference with
individual privacy. It is also essential in encouraging the health care workers ( either
infected or at risk of infection ) to receive proper counselling and management.

2.5 Currently there is no justification for restricting practice of health care workers on the
basis of the HIV status alone. Restriction or modification, if any, should be determined on a
case-by-case basis.

3. GUIDELINES

3.1 Enforcement of infection control

T h e b e s t w a y o f p r e v e n t i n g b l o o d - b o r n e d i s e a s e s i s t o t r e a t a l l b l o o d ( a n d certain
body fluids ) as potentially infectious. Universal precautionary measures should be adopted
w h e n h a n d l i n g b l o o d , a m n i o t i c fluid, pericardial fluid, pleural fluid, peritoneal fluid, synovial
fluid, cerebrospinal fluid, semen and vaginal secretion. The risk of HIV transmission from
faeces, saliva, nasal secretion, sputum, sweat, tears, urine and vomitus without overt blood
staining is extremely low, and good simple hygienic measures should be sufficient.

Sound infection control practice with appropriate quality assurance should be

implemented at all levels, taking into consideration factors unique to individual setting.

(a) Infection control committee

Rapid advancement in medicine and technology has meant that it is essential to keep
updated on issues relating to infection control practice. Infection control committees should
efficiently serve the functions of developing, promulgating and updating infection control
policies in each institution and for each clinical specialty.

(b) Written infection control guidelines

Written infection control guidelines on universal blood/body fluid precaution should

be developed and periodically updated in all health care settings - by infection control
committees or equivalents for institutions / government departments and by professional
bodies for health care professionals in private and solo practice.

129
(c) Infection control training

The subject of infection control should be made an integral part of undergraduate, pre-
registration or pre-employment training for all health care workers who may come into
contact with blood/body fluids. Similarly, regular courses tailored to the infection control
needs of individual specialties, should be organised by professional bodies,
universities/polytechnics as well as relevant government depart ments. It should be made
known that those who fail to use appropriate infection control techniques to protect patients
may be subject to charges of professional misconduct by the relevant governing body.

3.2 HIV counselling & related services for health care workers

Information and counselling should be made easily available for health care workers
who may have been exposed to HIV through risk behaviour, exposure to contaminated
blood/blood products or occupational accidents. The importance of voluntary, confidential
a n d a n o n y m o u s c o u n s e l l i n g a n d H I V t e s ti n g s h o u l d b e u n d e r l i n e d .

3.3 Rights & responsibilities of HIV infected health care workers

3.3.1 Confidentiality

In general, health care workers are not required to disclose their HIV status to their
employers or clients. HIV infection and AIDS are not notifiable diseases by law in Hong
Kong, and reporting is on a voluntary basis. There are, however, occasions where the HIV
status has to be made known on a need-to-know basis, and this will normally be with the
consent of the infected worker. For example, doctors or specialists involved in evaluating an
infected health care worker may need to know his HIV status. In exceptional circumstances,
breach of confidentiality may be warranted, for instance when an HIV infected health care
worker refuses to observe the restrictions and patients have been put at risk.

3.3.2 Right to work

The status and rights of an HIV-infected health care worker as an employee should be
safeguarded. If work restriction is required, employers should make arrangement for
alternative work, with provision for retraining and redeployment.

3.3.3 Ethical issues

An HIV-infected health care worker should seek appropriate counselling and to act
upon it when given. It is unethical if one fails to do so as patients are put at risk. The
attending doctor of an HIV-infected health care worker should seek the advice of the expert
panel formed by the Director of Health on the areas of management and possible need for
job modification. The doctor who has counselled an HIV-infected colleague on job
modification and who is aware that the advice is not being followed and patients are put at
risk, has a duty to inform the Medical / Dental Council for appropriate action.

3.3.4 Source of advice

130
 Referral to the expert panel should be made by the health care worker's attending
physician. Formed by the Director of Health, the panel shall decide on whether job modi-
fication, limitation or restriction is warranted. A case-by-case evaluation would be
undertaken considering multiple factors that can influence risk and work performance.

3.4 Responding to the public

The issue of HIV transmission in health care setting has caused much public concern
despite the minimal risk incurred. Focussing on health care setting in fact deflects the
society from proper attention to the major transmission routes through sex and drug abuse.
The health care profession has the duty of constantly reassuring the public, and to educate
the clients on how HIV can and cannot be contracted. More importantly, the public looks on
the health care profession as an example of how AIDS should be dealt with. By adhering to
the guidelines for prevention of HIV infection in the health care setting, public fear can be
allayed.

131
 Appendix I-A

*GLOBAL AIDS STATISTICS

(reported to the WHO as at 30 June 1995)

Continent No.
Africa 418051
Americas 580129
Asia 23912
Europe 141275
Oceania 6444
World Total 1169811

* The estimated cumulative AIDS cases in adults and children is 4.5 million while that of HIV
infection among adults and children is 18.5 million and 1.5 million respectively. The largest
number of HIV infection has ocurred in Sub-saharan Africa (>11 million), followed by South
and South-east Asia (3.5 million).

132
 Appendix I-B

*CUMULATIVE HIV/AIDS STATISTICS

IN HONG KONG
(reported to the Department of Health till 30 June 1995)

No. (%)#
Total AIDS
SEX Male 518 (90) 136 (92)
Female 55 (10) 12 (8)

ETHNICITY Chinese 380 (66) 101 (68)

Non-Chinese 193 (34) 47 (32)
Asians 46(8) 13 (9)
Whites 116(20) 32 (22)
Blacks 8(1) 2 (1)
Others 23(4) 0 (0)

RISK FACTORS Heterosexual 249 (43) 52 (35)

Homosexual 157 (27) 57 (39)
Bisexual 41 (7) 17 (11)
Injecting drug users 12 (2) 3 (2)
Transfusion recipients 66 (12) 12 (8)
Perinatal 2 (<1) 1 (<1)
Undetermined 46 (8) 6 (4)

TOTAL 573 148

* The estimated cumulative HIV and AIDS cases is 3000 and 250 respectively. The projected
number by the year 2000 is 8000-12000 and 1650-1800 for HIV and AIDS respectively.
# Percentage may not add up to 100 due to rounding off of figures.

133
 Appendix II
Organizational Structure
of Hong Kong AIDS Programme

Hong Kong
Government

Council for AIDS Trust Fund

Advisory Council on
AIDS
Subcommittees

Secretariat : Department of Health

Scientific Committee Committee on Education & AIDS Services

on Development
AIDS (SCA) Publicity on AIDS Committee (ASDC)
(CEPAIDS)

Planning/Evaluation
Subcommittee Working Groups
on

Social & Support Services

Clinical Services
Evaluation
Publicity Working Group
Working Group on
Youth
Working Group on Schools/Students
Working Group on Drug Abuse &
AIDS
Workplace Working
Group

Operational government departments

and public organizations
(major ones) :

Department of
Health
Information Services Department
Education
Department
[Hospital Authority]
Social Welfare Department
Council of Social Service

Non-governmental organizations :
(on AIDS) :

134
Hong Kong AIDS
Foundation
AIDS Concern
AIDS Memorial Quilt
Project
Society for AIDS
Care
HIV Information & Drop-in Centre

135
 Appendix III

SERVICES PROVIDED BY THE AIDS UNIT,

DEPARTMENT OF HEALTH

1. Telephone Counselling Service

The Service is composed of two systems - the AIDS counselling hotline and the
infoline. The AIDS hotline (Tel: 2780 2211) utilises an interactive voice processing
system. Callers may choose to listen to recorded AIDS or STD messages (24-hour
computerised system), or talk to experienced nurse-counsellor directly by selecting the
right number. HIV antibody tests and/or face-to-face counselling could be arranged if
required. Counsellors are available between 8 am to 8 pm, from Monday to Friday. All
information is kept in strictest confidence.

Computerised pre-recorded AIDS messages in Tagalog, Thai, and Vietnamese

are also available 24 hourly at Tel: 2359 9112. Advice for health care workers on
occupational exposure to body substance can be accessed through the infolines of
2359 9115 (English) and 2770 1147 (Chinese).

2. Face-to-face Counselling and HIV Screening Service

The service provides in-depth face-to-face counselling, and HIV antibody tests
to people at risk of infection. It is free, strictly confidential and anonymous.
Appointment has to be made in advance.

3. Consultation and Clinical Service

Counselling and consultation are available to HIV-infected individuals. The Unit

takes referrals from different sources e.g. Social Hygiene Clinics, Hong Kong Red
Cross Blood Transfusion Service, public hospitals/clinics, private doctors and self
referral. Medical personnel can call for advice (2780 8622) whenever necessary. HIV-
infected individuals are given clinical and laboratory assessment regularly in addition
to psychological support. Treatment and prophylaxis programmes are prescribed at the
unit's Special Medical Clinic when required. Again, all the information is kept in
strictest confidence and anonymity is ensured.

4. Health Education Activities

The service is responsible for organising health education activities on AIDS

including seminars, workshops, lectures, health talks and exhibitions. It operates as an
important executive arm of the Committee on Education & Publicity on AIDS, in
collaboration with other government (e.g. Methadone clinics, Information Services
Department, Education Department, Correctional Services Department, Social Welfare
Department) and non-governmental organisations. The Community Charter on AIDS is

136
 a new initiative developed together with Lions International Hong Kong. A newsletter
is published 3 times a year covering various issues relating to HIV infection.

5. AIDS Resource Centre

The service keeps a collection of a good variety of both local and overseas
education materials, for medical professionals and the public who are interested in
AIDS care, education and publicity. Materials available include books, journals, audio-
visuals, pamphlets, posters and resource kits.

6. Research Activities and Evaluation Programmes

The Unit has been actively involved in research relating to various aspects of
HIV/AIDS with local perspective and relevance. Some topics that have been covered
include clinical manifestation and management, epidemiology, AIDS-related
behaviours/attitudes, and effectiveness of local health education activities.

7. Epidemiology and Surveillance

In collaboration with the Scientific Committee on AIDS and the government

Virus Unit, the AIDS Unit undertakes regular surveillance activities to monitor the local
HIV/AIDS situation. It collects data for the voluntary HIV/AIDS reporting system in
Hong Kong, and operates the AIDS Scenario & Surveillance Research programme
together with the University of Hong Kong. A Hong Kong STD/AIDS update is
published quarterly, in conjunction with the Social Hygiene Service of the Department
of Health, to keep professionals and interested parties abreast of the local trend.

137
 Appendix IV

*CLASSIFICATION FOR HIV INFECTION AND

SURVEILLANCE CASE DEFINITION FOR AIDS IN
ADULTS & ADOLESCENTS IN HONG KONG (1995)

CD4+ T-cell (A) (B) (C)

categories Asymptomatic, Symptomatic, not (A) AIDS-indicator
acute (primary) or (C) conditions conditions
HIV or PGL
(1) ≥ 5 0 0 / u l A1 B1 C1
(2) 200-499/ul A2 B2 C2
(3) < 200/ul - AIDS A3 B3 C3
indicator T-cell
count
NB
• Categories are defined by both CD4 count and clinical presentation.
• H o n g K o n g e m p l o y s o n l y A I D S - d e f i n i n g diseases b u t n o t t h e i m m u n o l o g i c a l c r i t e r i a o f
CD4 <200/ul as surveillance case definition for AIDS, which is different from the 1993
CDC AIDS surveillance definition. Also diseases included in category C were modified.
• Where there is an overlap of conditions, (C) takes precedence over (B), which takes
precedence over (A).
• For classification purposes, once a Category C condition has occurred, the person will
remain in Category C.

Category A
Asymptomatic HIV infection
Persistent generalised lymphadenopathy
Acute (primary) HIV infection with accompanying illness or history of acute HIV infection

C a t e g o r y B (include the following, but not limited to)

Bacillary angiomatosis
Candidiasis, oropharyngeal (thrush)
Candidiasis, vulvovaginal; persistent, frequent, or poorly responsive to therapy
Cervical dysplasia (moderate or severe)/ cervical carcinoma in situ
C o n s t i t u t i o n a l s y m p t o m s , s u c h a s f e v e r ( 3 8 . 5 0C ) o r d i a r r h o e a l a s t i n g > 1 m o n t h
Hairy leucoplakia, oral
Herpes zoster (shingles), involving at least two distinct episodes or more than one
dermatome
Idiopathic thrombocytopaenia
Listeriosis
Pelvic inflammatory disease, particularly if complicated by tubo-ovarian abscess
Peripheral neuropathy

138
#C a t e g o r y C :AIDS indicator conditions
Candidiasis of bronchi, trachea, or lungs
Candidiasis , oesophageal
Cervical cancer, invasive
Coccidioidomycosis, disseminated or extrapulmonary
Cryptococcosis, extrapulmonary
Cryptosporidiosis, chronic intestinal (> 1 month's duration)
Cytomegalovirus disease (other than liver, spleen, or nodes)
Cytomegalovirus retinitis ( with loss of vision )
Encephalopathy, HIV-related
Herpes simplex: chronic ulcer(s) ( > 1 month's duration ); or bronchitis, pneumonitis, or
oesophagitis
Histoplasmosis, disseminated or extrapulmonary
Isosporiasis, chronic intestinal ( > 1 month's duration )
Kaposi's sarcoma
Lymphoma, Burkitt's ( or equivalent term )
Lymphoma, immunoblastic ( or equivalent term )
Lymphoma, primary, of brain
Mycobacterium avium complex or M kansasii, disseminated or extrapulmonary
Mycobacterium tuberculosis; extrapulmonary or pulmonary/cervical lymph node (only if
CD4 <200/ul)
Pneumonia, recurrent
Penicilliosis, disseminated
Mycobacterium, other species or unidentified species, disseminated or extrapulmonary
Pneumocystis carinii pneumonia
Progressive multifocal leukoencephalopathy
Salmonella septicaemia, recurrent
Toxoplasmosis of brain
Wasting syndrome due to HIV

#M o d i f i c a t i o n of the CDC 1993 AIDS surveillance case definition: (1) Penicilliosis has been
added and (2) pulmonary or cervical lymph node tuberculosis included only if CD4 <200/ul

*adapted from the 1993 CDC revised classification system for HIV infection and expanded
surveillance case definition for AIDS among adolescents and adults (MMWR 1992;Vol 41:1-
4,15), and endorsed by the Advisory Council on AIDS in July 1995.

139
 Appendix V

*CLASSIFICATION SYSTEM FOR HIV INFECTION

IN CHILDREN LESS THAN 13 YEARS OF AGE
IN HONG KONG (1995)

Paediatric human immunodeficiency virus ( HIV) classification φ

Clinical categories
Immunologic N: No signs/ A: Mild signs/ B: Moderate C: Severe
categories symptoms symptoms signs/ signs/
symptoms symptoms
1: No evidence of
suppression N1 A1 B1 C1
2: Evidence of
moderate N2 A2 B2 C2
suppression
3: Severe N3 A3 B3 C3
suppression

φ Children whose HIV infection status is not confirmed are classified by

using the above grid with a letter E (for perinatally exposed) placed before
the appropriate classification code (e.g., EN2)

Immunologic categories based on age-specific CD4+ T-lymphocyte counts

and percent of total lymphocytes

Age of child
<12 mos 1-5 yrs 6-12 yrs
Immunologic category uL (%) uL (%) UL (%)
1: No evidence of ≥ 1,500 ( ≥ 25) ≥ 1,000 ( ≥ 25) ≥ 500 ( ≥ 25)
suppression
2: Evidence of moderate 750- 500- 200-
suppression 1,499 (15-24) 999 (15-24) 499 (15-24)
3: Severe suppression <750 (<15) <500 (<15) <200 (<15)

140
Clinical categories for children with human immunodeficiency virus (HIV) infection

CATEGORY N: NOT SYMPTOMATIC

Children who have no signs or symptoms considered to be the result of HIV infection
or who have only one of the conditions listed in Category A.

CATEGORY A: MILDLY SYMPTOMATIC

Children with two or more of the conditions listed below but none of the conditions
listed in Categories B and C.
• Lymphadenopathy (≥ 0.5 cm at more than two sites; bilateral = one site)
• Hepatomegaly
• Splenomegaly
• Dermatitis
• Parotitis
• Recurrent or persistent upper respiratory infection, sinusitis, or otitis media

CATEGORY B: MODERATELY SYMPTOMATIC

Children who have symptomatic conditions other than those listed for Category A
or C that are attributed to HIV infection. Examples of conditions in clinical Category B
include but are not limited to :

• A n a e m i a ( < 8 g m / d L ) , neutropaenia (< 1,000/mm3) , o r t h r o m b o c y t o p a e n i a ( <

100,000/mm3) p e r s i s t i n g ≥3 0 d a y s
• Bacterial meningitis, pneumonia, or sepsis (single episode)
• Candidiasis, oropharyngeal (thrush), pers isting (> 2 months) in children >6
months of age
• Cytomegalovirus infection, with onset before 1 month of age
• Diarrhoea, recurrent or chronic
• Hepatitis
• Herpes simplex virus (HSV) stomatitis, recurrent (more than two episodes
within 1 year)
• HSV bronchitis, pneumonitis, or oesophagitis with onset < 1 month of age
• Herpes zoster (shingles) involving at least two distinct episodes or more
than one dermatome
• Leiomyosarcoma
• Lymphoid interstitial pneumonia (LIP) or pulmonary lymphoid hyperplasia
complex
• Nephropathy
• Nocardiosis
• Persistent fever (lasting > 1 month)
• Toxoplasmosis, onset before 1 month of age
• Varicella, disseminated (complicated chickenpox)

CATEGORY C: SEVERELY SYMPTOMATIC

Children who have any condition listed in the 1987 surveillance case definition for
acquired immunodeficiency syndrome, with the exception of LIP.

141
Conditions included in clinical Category C for children infected with human
immunodeficiency virus (HIV)

CATEGORY C: SEVERELY SYMPTOMATIC

• Serious bacterial infections, multiple or recurrent (i.e. any combination of at least two
culture-confirmed infections within a 2-year period), of the following types :
septicaemia, pneumonia, meningitis, bone or joint infection, or abscess of an internal
organ or body cavity (excluding otitis media, superficial skin or mucosal abscesses, and
indwelling catheter-related infections)
• Candidiasis, oesophageal or pulmonary (bronchi, trachea, lungs)
• Coccidioidomycosis, disseminated (at site other than or in addition to lungs or cervical
or hilar lymph nodes)
• Cryptococcosis, extrapulmonary
• Cryptosporidiosis or isosporiasis with diarrhoea persisting > 1 month
• Cytomegalovirus disease with onset of symptoms at age > 1 month (at a site other than
liver, spleen, or lymph nodes)
• Encephalopathy (at least one of the following progressive findings present for at least
2 months in the absence of a concurrent illness other than HIV infection that could
explain the findings) : a) failure to attain or loss of developmental milestones or loss of
intellectual ability, verified by standard developmental scale or neuropsychological
tests; b) impaired brain growth or acquired microcephaly demonstrated by head
circumference measurements or brain atrophy demonstrated by computerised
tomography or magnetic resonance imaging (serial imaging is required for children <2
years of age); c) acquired symmetric motor deficit manifested by two or more of the
following: paresis, pathologic reflexes, ataxia, or gait disturbance
• Herpes simplex virus infection causing a mucotaneous ulcer that persists for > 1
month's duration; or bronchitis, pneumonitis, or oesophagitis for any duration affecting
a child >1 month of age
• Histoplasmosis, disseminated (at a site other than or in addition to lungs or cervical or
hilar lymph nodes)
• Kaposi's sarcoma
• Lymphoma, small, noncleaved (Burkitt's), or immunoblastic or large cell lymphoma or B-
cell or unknown immunologic phenotypes
• Lymphoma, primary, of brain
• Mycobacterium avium complex or M kansasii, disseminated (at a site other than or in
addition to lungs or cervical or hilar lymph nodes)
• Mycobacterium tuberculosis; disseminated or extrapulmonary; if pulmonary or cervical,
patients need to be in immunologic category of severe suppression
• Mycobacterium, other species or unidentified species, disseminated (at a site other than
or in addition to lungs or cervical or hilar lymph nodes)
• Pneumocystis carinii pneumonia
• Progressive multifocal leukoencephalopathy
• Salmonella (nontyphoid) septicaemia, recurrent
• Toxoplasmosis of brain with onset >1 month of age
• Wasting syndrome in the absence of a concurrent illness other than HIV infection that
could explain the following findings: a) persistent weight loss 10% of baseline OR b)

142
 downward crossing of at least two of the following percentile lines on the weight for
age chart (e.g. 95th, 75th, 50th, 25th, 5th) in a child ≥ 1 year of age OR c) <5th percentile
f o r w e i g h t - f o r - h e i g h t c h a r t o n t w o c o n s e c u t i v e m e a s u r e m e n t s , ≥3 0 d a y s a p a r t P L U S a )
c h r o n i c d i a r r h o e a ( i . e . a t l e a s t t w o l o o s e s t o o l s p e r d a y f o r ≥3 0 d a y s ) O R b ) d o c u m e n t e d
fever(for ≥3 0 d a y s , i n t e r m i t t e n t o r c o n s t a n t )

• Penicilliosis, disseminated

*adapted from the 1994 CDC revised classification system for human immunodeficiency
virus infection in children less than 13 years old (MMWR 1994;43RR-12), and endorsed by
the Advisory Council on AIDS in July 1995.

143
 Appendix VI

LIST OF LOCALLY-PREPARED DOCUMENTS

ON HIV/AIDS

A. Professional guidelines and protocols established by the Advisory

Council on AIDS and its committees

B. Guidelines and other publications prepared by government

departments

C. Reports and information papers of the Advisory Council on AIDS

A. List of professional guidelines and protocols

established by the Advisory Council on AIDS
and its committees

1. H o s p i t a l m a n a g e m e n t o f H I V i n f e c t e d i n d i v i d u a ls - Scientific Working Group on AIDS 1990

2. Virus inactivation for clotting factor concentrates - Scientific Working Group on AIDS 1991

3. Disease notification in the context of HIV/AIDS - Scientific Working Group on AIDS 1992

4. G u i d e l i n e s o n C o n s en t f o r H I V t e s t i n g - Scientific Working Group on AIDS 1992

5. Procedures for management of needlestick injury or mucosal contact with blood or body
fluids : recommended guidelines for HIV and hepatitis B prevention - Scientific Working
Group on AIDS and Scientific Working Group on Viral Hepatits Prevention 1992, revised in
1995 ( H e p a t i t i s C p r e v e n t i o n i n c l u d e d )

6. Prevention of transmission of HIV in health care settings : guidelines and practices -

Scientific Working Group on AIDS 1992, Scientific Committee on AIDS 1995

7. HIV & AIDS : Information for primary care doctors - Committee on Education and Publicity
on AIDS 1992

8. Proposed revised specification for clotting factor concentrates - Scientific Working Group
on AIDS 1993

144
9. Recommended guidelines for undertaking anonymous screening for public health
surveillance of HIV infection in Hong Kong - Scientific Working Group on AIDS 1993

10. HIV infection and health care workers : recommended guidelines - Advisory Council on
AIDS 1994

11. Guidelines on management of HIV infection in children - Scientific Committee on AIDS

1994, 1995

12. HIV antibody testing : recommended measures to generate quality results - Scientific
Committee on AIDS 1994

13. The choice of safe clotting factor concentrates for treatment of haemophilia in Hong
Kong : recommended guidelines - Scientific Committee on AIDS 1994

B . List of guidelines and other publications prepared by

government departments

1. Prevention of blood-borne diseases in schools - Medical & Health Department and

Education Department 1987 [Chinese & English]

2. Information on AIDS for doctors and dentists - Medical & Health Department 1987,
Department of Health 1992

3. Information on AIDS for nurses - Medical & Health Department 1988, Department of Health
1993 [Chinese & English]

4. Principles of hospital management of HIV infected individuals - Hospital Services

Department 1991

5. HIV/AIDS report form DH2293 - Department of Health 1992

6. Laboratory tests for AIDS (circular) - Department of Health 1992, 1994

7. Guidelines on issues relating to HIV-positive pupils in schools (administrative circular) -

Education Department 1994

8. Guidelines on the prevention of blood-borne diseases in schools - Department of Health

and Education Department 1994 [Chinese & English]

9. Guidelines on infection control practice in clinics and maternity homes - Infection Control
Committee of Department of Health 1993

145
10. Guidelines on infection control practice in dental clinics - Infection Control Committee of
Department of Health 1994

Department of Health, Hospital

11. P r e c a u t i o n s f o r h a n d l i n g a n d d i s p o s a l o f d e a d b o d i e s -
Authority, Urban Services Department, Regional Services Department 1994[Chinese & English]

C . List of reports and information papers of the

Advisory Council on AIDS

1. Strategies for AIDS prevention, care and control in Hong Kong - July 1994

2. A review of services provided to people with HIV/AIDS in Hong Kong - AIDS Services
Development Committee July 1994

3. Evaluation of educational pro grammes on AIDS in secondary schools in Hong Kong -

Committee on Education and Publicity on AIDS July 1994

4. *Report of the study group on HIV infection of haemophiliacs through blood products
in Hong Kong (submitted to the Health & Welfare Branch) - May 1993

5. *Estimation and projection of HIV infection and AIDS cases in Hong Kong - report of
the AIDS Scenario & Surveillance Research Project, initiated and monitored by the
Scientific Committee on AIDS 1994

6. Prevention and management of tuberculosis in HIV-infected patients: an information

paper - Scientific Committee on AIDS 1995

7. Classification system for HIV infection and surveillance case definition for AIDS in
adolescents and adults in Hong Kong - Scientific Committee on AIDS 1995

* NOT an ACA (Advisory Council on AIDS) paper

146
 Appendix VII

ETHICAL GUIDELINES ON AIDS BY THE HKMA/BMA

JOINT ETHICS ADVISORY COMMITTEE

A. Treatment of AIDS patients

(published in HKMA Newsletter, January 1989)

The following statements on treatment of AIDS patients was adopted at the 40th
World Medical Assembly in September 1988. The Joint Ethics Advisory Committee of the
Medical Association and the British Medical Association (Hong Kong Branch) has adopted
them as its position and would like to advise members accordingly.

"Patients with AIDS and those who test positively for the antibody to the AIDS virus
must be provided with appropriate medical care and should not be treated unfairly or suffer
from arbitrary or irrational discrimination in their daily lives. Physicians have a long and
honored tradition of tending to patients afflicted with infectious diseases with compassion
and courage. That tradition must be continued throughout the AIDS epidemic.

A I D S p a t i e n t s a r e e n t i t l e d t o c o m p e t e n t m e d i c a l c a re w i t h c o m p a s s i o n a n d r e s p e c t f o r
human dignity. A physician may not ethically refuse to treat a patient whose condition is
within the physician's current realm of competence, solely because the patient is
seropositive. Medical ethics do not permit categorical discrimination against a patient based
solely on his or her seropositivity. A person who is afflicted with AIDS needs competent,
compassionate treatment. A physician who is not able to provide the care and services
required by persons with AIDS should make an appropriate referral to those physicians or
facilities that are equipped to provide such services. Until the referral can be accomplished,
the physician must care for the patient to the best of his or her ability."

B. AIDS and Confidentiality

(published in HKMA Newsletter, March 1989)

The HKMA/BMA Joint Ethics Advisory Committee discussed the position on AIDS
and Confidentiality and has reached the following opinion :

" P a t i e n t s , t h e i r c o n t a c t , t h e M e d i c a l P r o f e s s i o n a n d t h e c o m m o n g o o d are most likely

to be best served, if the tradition of confidentiality continues to be honored. The
requirement for confidentiality therefore is a strong obligation. However, it is acknowledged
that there may be some exceptional circumstances when a doctor may feel obliged to
disclose information to third parties who may be put at SERIOUS RISK. This disclosure may
only be considered after all reasonable efforts have been made on the part of the attending
doctor to counsel the patient on the necessity for the patient to take steps to protect third
parties who may be put at SERIOUS RISK. Under these circumstances when information is
disclosed to third parties the doctor must be able to justify his actions."

147
C. AIDS Testing
(published in HKMA Newsletter, November/December 1989)

The HKMA/BMA Joint Ethics Advisory Committee has discussed the issue of
whether consent is required for testing for HIV antibody and would like to present the
following views for members' consideration :

1. I t i s g e n e r a l l y a c c e p te d a n d w e l l u n d e r s t o o d w i t h i n t h e p r o f e s s i o n t h a t a d o c t o r
should treat a patient only on the basis of the patient's informed consent. A
patient's consent may be given implicitly, for example by agreement to provide a
specimen of blood for routine multiple analysis. Under other circumstances, explicit
consent may be required, for example before undergoing a specific operative
procedure.

2. Whether implicit or explicit consent is required for HIV antibody testing depends
on what patients actually consent to when presenting themselves to the medical
practitioner for medical treatment. One view is that when patients present
themselves for treatment, consent is implied for the medical practitioner to carry out
the necessary investigations which are necessary for management and are in the
best interest of the patient. Another view is, because HIV infection has such
serious social and financial consequences, HIV antibody testing should not be
regarded as a "routine test" and explicit consent should be sought. Whichever
view prevails, the doctor in carrying out such tests must act in the best interest of
the patient.

(Remarks : The Committee noted that the legal adviser of BMA concluded that as
the law stood at present the consent of the patient was essential and that it would
be unwise for doctors to adopt a course that would expose them to the possibility
of criminal and civil proceedings.)

3. Circumstances may occasionally arise where it may not be possible to obtain

consent due to the patient being unconscious or unfit to give consent and where
the treatment is necessary for the protection of life or the preservation of the health
of patients. The practitioner may under such situations proceed to test for HIV
antibody without obtaining prior consent.

4. In the most exceptional circumstance, where a test is imperative in order to secure

the safety of persons other than the patient, testing without explicit consent may
be justified. Attempts should always be made to obtain the prior consent of the
patient if practicable. Because of the low risk of nosocomial HIV infection to health
personnel and the need to adopt universal blood precautions in any case, in
laboratories and operating theatres, routine testing for HIV antibodies for patients
does not fall under this category.

148
 Appendix VIII

DISINFECTION PROCEDURES TO PREVENT

TRANSMISSION OF HIV IN HEALTH CARE SETTINGS

Disinfection is best achieved by physical methods such as boiling. Low temperature

steam and pasteurisation at temperature 65o C for 30 minutes or 80o C for 10 minutes are also
effective.

Chemical disinfection is inherently complicated because of the variety of factors that

influence the antimicrobial activity of disinfectants. Wherever possible, disinfectants should
only be used on clean surfaces as they may fail to penetrate overlying soil such as blood or
pus on instruments.

In routine situations, the most useful chemical disinfectants are hypochlorite, ethyl
alcohol and glutaraldehyde.

1. Chlorine - sodium hypochlorite

Properties:
• Wide range of bactericidal, fungicidal and virucidal activity.
• Disinfectant of choice for use against viruses, including hepatitis B virus and
HIV.
• R a p i d a c t io n .
• Moderate to severe inactivation by organic matter.
• Incompatible with cationic detergents.
• Dilute hypochlorite solutions decay rapidly and should be made up daily.
• Not to mix with acid.
• Not to be used in the presence of formaldehyde.
• Corrosive to metal (especially 1:10 or higher concentration).

149
 Uses of Hypochlorites and Strength of Solutions

USES Dilution of stock Available chlorine Minimum duration

solution* (clorox) (PPM) of exposure
Undiluted (5.25%) 50,000#

Large blood spillage 1:5 10,000 30 min

or
presence of gross organic
matter

Laboratory pipette jars 1:10 5,000 30 min

and
general blood spillage

General disinfection and 1:50 1,000 30 min

small blood spillage

* Care is required in preparation of the solution as the amount of available chlorine in stock
solution varies with the country of manufacture, e.g. household bleach 'clorox' in USA and Canada
(5.25% available chlorine), Eau de Javel in France (15% available chlorine), 'Chloros' in the United
Kingdom (10-15% available chorine).

# Approximate values

2. Alcohol - Ethanol, isopropanol

Properties:
• Good bactericidal and fungicidal activity.
• Virucidal against most categories of viruses.
• Rapid in action.
• Poor penetration into organic matter, e.g. pus and blood.
• Volatile.

Usual concentration: 70%

Uses:
• Skin disinfection
• Disinfection of physically c lean inanimate surfaces such as trolley tops.

3. Glutaraldehyde - Cidex, Totacide

Properties:
• Wide range of bactericidal, fungicidal and virucidal activity.
• Non-corrosive to metals and o ther materials.
• Little inactivation by organic matter, but penetrates slowly.
• Alkaline solutions require activation and have a limited useful life (14-28 days).
• Irritant to eyes, skin and respiratory mucosa.
• Toxic to tissue, need final rinse with sterile water.

150
 Usual concentration: 2%
Uses:
• Disinfection of equipment that cannot be heat-s terilised.

Other commonly available disinfectants are briefly described below:

(a) Formaldehyde - Formalin (37% formaldehyde in water)

Formaldehyde in water is a powerful disinfectant for a contaminated surface and

instrument, but it is too irritant to be used as a general disinfectant.

4% formaldehyde overnight is used for disinfecting the dialysis fluid pathways

of the haemodialysis machine.

(b) Phenolics - printol, lysol

Phenolics have some virucidal activity and results of in vitro tests have shown
that lysol is capable of inactivating HIV. For blood spillage onto surfaces or
contaminated heat-sensitive articles, use may be made of 2% phenolic disinfectants.
For general enviromental hygiene practice, 1% phenolic disinfectant is recommended.

Dettol is not effective in killing HIV.

(c) Diguanides - chlorhexidine

Diguanides have little activity against viruses.

(d) Hydrogen peroxide and ethylene oxide are also capable of inactivating HIV.

References :

1. Second meeting of the WHO Collaborating Centres on AIDS: Memorandum from a

WHO meeting. Bulletin of the World Health Organization 1986; 84(1):37-46.

2. Chemical Disinfection in Hospitals by G A J Ayliffe et al. Public Health Laboratory

Service, London, 1984.

3. Recommended Infection-control pra ctices for Dentistry. MMWR 1986; Vol 35:No. 15.

4. Advisory Committee on Dangerous Pathogens, Health and Safety Commission,

UK:LAV/HTLV III - the causative agent of AIDS and related conditions - Revised
guidelines, June 1986.

5. Recommendations for pre vention of HIV transmission in health-care settings. MMWR

1987; Vol 36:No. 2S.

6. Guidelines for Prevention of Transmission of HIV and HBV to Health-care and Public
S a f e t y W o r k e r s . MMWR 1989; Vol 38:No. S-6.

151
 Appendix IX

LIST OF INFECTIOUS DISEASES REQUIRING

SPECIAL DISPOSAL PROCEDURES FOR DEAD
BODIES

1. Anthrax

2. Human immunodeficiency virus infection

3. Plague

4. Rabies

5. Viral haemorrhagic fevers

6. Other infectious diseases as deemed necessary by the physician i/c, the infection
control officer or microbiologist

152
 Appendix X

ADVICE TO STAFF OF FUNERAL PARLOURS AND

RELATIVES ON THE SAFE HANDLING OF DEAD
BODIES WITH INFECTIOUS DISEASES

This is to inform you that the deceased had suffered from infectious
diseases. The body had been enclosed in a plastic bag. For safe handling of the body, you
are advised to adopt the followings :

(1) There should be minimal handling of the deceased's body.

(2) The body should not normally be removed from the plastic bag.

(3) Embalming is not recommen d e d .

(4) Viewing of the face without physical contact should be permitted. The
plastic bag should be resealed afterwards.

(5) Avoid direct contact with blood or body fluids from deceased's body.

(6) Persons handling the body should wear disposable gloves and protective
clothing. After use, these gloves and clothing should be soaked in
freshly prepared household bleach (1:50 dilution) for 30 min. before
washing or disposal.

(7) Hands must be thoroughly washed after removing gloves and protective
clothing.

(8) Relatives who are worried about having already exposed to the infection
should contact the physician i/c for counselling.

153
 Appendix XI

USEFUL TELEPHONE NUMBERS

1. AIDS Unit, Department of Health

AIDS Hotline 2780 2211
(24-hour computerised recorded messages
in English, Cantonese, Putonghua)
(Nurse telephone counselling service,
Monday - Friday; 8:00 a.m. - 8:00 p.m.)

Seropositive individuals 2780 3289

(Monday - Friday; 8:00 a.m. - 8:00 p.m.)

24-hour c omputerised recorded messages 2359 9112

in Tagalog, Thai and Vietnamese

Infoline (recorded messages) for health care workers on Needlestick Injury

Cantonese 2770 1147
English 2359 9115

2. Special Medical Clinic, Department of Health

For medical personnel 2780 8622

3. Advisory Council on AIDS Secretariat 2961 8550

4. HIV Antibody test (Virus Unit, QMH)

Dr. WL Lim, Consultant 2855 4112
Enquiries 2855 4121

5. T-lymphocyte test (Pathology Institute, Yan Oi Polyclinic)

Dr. CS Feng, Consultant 2458 9311 (Ext. 257 & 202)
Enquiries 2458 9311 (Ext. 257, 263 & 206)

6. Social Hygiene Clinics - m a j o r o n e s a r e

• Hong Kong region :
Tang Shiu Kin Social Hygiene Clinic 2831 6846, 2831 6853
• Kowloon region :
Yaumatei Social Hygiene Clinic 2359 4377, 2388 6634
Yung Fung Shee Social Hygiene Clinic 2727 8315
• New Territories :
South Kwai Chung Social Hygiene Clinic 2421 4010
Tuen Mun Social Hygiene Clinic 2459 2958

treatment is free; no referral or appointment is needed; all information is kept confidential; HIV
testing is offered for people suspected/confirmed of having STDs

154
7. Hong Kong AIDS Foundation office 2560 8528
helpline 2513 0513

8. AIDS Concern service centre 2898 4411

helpline 2898 4422
(every Thursday and Saturday 7pm-10pm)

9. Action for REACH OUT 27770 1002

(every Monday and Thursday 7pm-10pm)

1 0 . AIDS Project, the Hong Kong Council of Social Service 2864 2963

11. HIV Information & Drop-in Centre 2501 0653

12. Hong Kong 10% Club 2314 8726

13. Hong Kong AIDS Memorial Quilt Project 2866 1887

14. Horizons Gay and Lesbian Hotline 2893 0208, 2893 0209
(every Tuesday & Thursday 7:30 - 10:30 pm)

15. Society for AIDS Care 2559 5205

155
 Appendix XII

ABBREVIATIONS & GLOSSARY

ADC AIDS Dementia Complex.

AIDS Acquired Immunodeficiency Syndrome.

See Appendix IV and V for definition.

ARC AIDS-related complex.

A loosely defined term to label patients who are symptomatic but
have not yet progressed to AIDS. It is much less commonly used
nowadays.

AZT Azidothymidine, Zidovudine (ZDV), Retrovir.

The first antiviral drug approved for use in HIV infection, see
Chapter 5.2.

β 2-microglobulin A protein that forms part of the MHC Class I molecule. An elevation
o f β2 - m i c r o g l o b u l i n i n s e r u m m a y i n d i c a t e d i s e a s e p r o g r e s s i o n .

Same as T4 or T-helper lymphocyte. It is the major target cell for HIV.

CD4 Immune dysfunction can be demonstrated by a low CD4 count,
CD4/CD8 ratio or CD4%. See Chapter 3.

Same as T8 or T-suppressor lymphocyte.

CD8
Centers for Disease Control in Atlanta, USA. It was renamed Centers
CDC for Disease Control and Prevention in 1992.

Cytomegalovirus.
CMV
Dideoxycytidine (Zalcitabine), a reverse transcriptase inhibitor. See
ddC Chapter 5.2.

Dideoxyinosine (Videx, didanosine), a reverse transcriptase inhibitor.

ddI See Chapter 5.2.

Ganciclovir. An antiviral drug useful for treatment of CMV infection.

DHPG
Epstein-Barr Virus. One of the factors causing non-Hodgkin's
lymphoma and oral hairy leucoplakia.
EBV

156
ELISA Enzyme - linked Immunosorbent Assay.
A common immunoassay system, usually used for antigen or
antibody detection.
A common technique used to screen for HIV antibody.

gag Core protein of HIV.

gp Glycoprotein.
Gp 120 is a glycoprotein with molecular weight of 120,000, found on
the surface of HIV.

HIV Human immunodeficiency virus.

(previously known as HTLV-III, LAV or ARV).

IFN Interferon.
A naturally-occuring or synthetic protein molecule that has
antiviral/immunomodulatory effects.

ICL Idiopathic CD4+ T lymphocytopaenia.

An immunologically, epidemiologically and clinically heterogeneous
condition with diminished CD4 count but negative HIV antibody
test. It is rare and can be associated with opportunistic
complications similar to that of AIDS.

KS Kaposi's sarcoma.
A vascular tumour that is common in HIV-infected homosexuals. see
Chapter 4.

LIP Lymphocytic interstitial pneumonia.

A clinical entity commonly associated with paediatric HIV infection.

Mycobacterium avium complex.

MAC S a m e a s M A I ( Mycobacterium avium-intracellulare).

Multi-drug resistant tuberculosis.

MDR TB
Multiple opportunistic pathogen prophylaxis.
MOPP A regimen of simultaneously protecting against several
opportunistic infections, preferably with single antimicrobe or as few
as possible.

Oral candidiasis.
OC
Opportunistic infection.
OI
Abbreviation for HIV core protein. p24 means a protein with MW of
p 24,000.
PCP Pneumocystis carinii p n e u m o n i a .
A very common AIDS-defining illness which however has effective
prophylaxis.

PCR Polymerase chain reaction.

A new technique for amplifying amounts of DNA, which can be
useful in detection of HIV in difficult situation.

PML Progresssive multifocal leucoencephalopathy.

RT Reverse transcriptase.
An enzyme critical for the replication of RNA virus.

T cells Lymphocytes derived from Thymus (T).

UAS Unlinked anonymous screening. The testing of markers of infection

(e.g. HIV infection) after elimination of all personal identifying
information from each specimen. This is useful in that participation
bias is reduced for the target group tested.

VDRL "Venereal Disease Research Laboratory" Test.

A screening test for syphilis.

VZV Varicella zoster virus.

The virus causing chickenpox and herpes zoster.

WB Western Blot test.

A specific immunological technique. Often used as confirmatory test
to validate the results of ELISA for HIV infection.

ZDV Zidovudine.
See AZT.

158
 Appendix XIII

SUGGESTED GENERAL READINGS

1. A Color Atlas of AIDS 1986. C F Farthing, SE Brown, RCD Staughton, J J Cream, M

Miihlemann. Wolfe / Year Book 1986.

2. Gu i d e l i n e s f o r P r e v e n t i o n o f T r a n s m i s s i o n o f H I V a n d H B V t o h e a l t h - c a r e a n d p u b l i c -
s a f e t y w o r k e r s . MMWR 1989; Vol 38: No. S-6.

3. AIDS Pocket Picture Guide 1989. I Williams, A Mindel, IVD Weller. Triton Biosciences
Inc.

4. Public Health Service Statement on Management of Occupational Exposure to HIV,

including Consideration regarding Zidovudine Postexposure Use. MMWR 1990; Vol. 39:
no. RR-1.

5. AIDS Clinical Review 1991 P. Volberding, MA Jacobson.

6. R e c o m m e n d a t i o n s f o r p r e v e n t i n g T r a n s m i s s i o n o f H IV a n d H e p a t i t i s B v i r u s t o p a t i e n t s
during Exposure - Prone Invasive Procedures. MMWR 1991; Vol. 40:no. RR-8.

7. 1993 revised classification system for HIV infection and expanded case definition for
AIDS among adolescents and adults. MMWR 1992; Vol 41: no. RR-17

8. The Medical Management of AIDS. 3rd edition 1993. Merle A. Sande and Paul A.
Volberding. W.B. Saunders.

9. HIV infection and AIDS - The Ethical Considerations. June 1993 General Medical
Council.

1 0 . A I D S - i m a g e s o f t h e e p i d e m i c . W o r l d H e a lt h O r g a n i z a t i o n 1 9 9 4

11. The HIV/AIDS Pandemic - 1994 overview. Global Programme on AIDS, World Health
Organization WHO/GPA/TCO/SEF/94.4 1994.

12. Recommendations of the US Public Health Service Task Force on the use of zidovudine
to reduce perinatal transmission of HIV. MMWR 1994; Vol 43: no. RR-11

13. 1994 revised classification system for HIV infection in children less than 13 years of age.
MMWR 1994; Vol 43: no. RR-12

159
 Appendix XIV
DEPARTMENT OF Health
HIV/AIDS Report Form

for office use

Please read the following instructions:
1. This is a voluntary report form for reporting
(i) newly diagnosed HIV infection;
(ii) newly diagnosed AIDS;
(iii) change(s) of status of previously diagnosed HIV/AIDS cases.
2. Only sections (A) & (C) need to be completed for reporting HIV Infection.
3. All sections, (A), (B) and (C) must be completed for reporting AIDS or updating information.
4. All individual information will be treated as strictly confidential and used in global analysis only.
5. Please mail the completed form to: Consultant Physician
Special Preventive Programmes
Department of Health
5/F Yaumatei JCC
145 Battery Street, Kowloon

Section (A) Reporting HIV Infection

Clinic/Hospital
Identification Reference no.: (HK resident/non-
Code : resident*)
Sex: M / F * Date of birth: or age (at last
(DD/MM/YY) birthday):
Ethnicity: Chinese / non-Chinese (specify country of )*
origin
Date of (laboratory) diagnosis:
(DD/MM/YY)
Name of Western Blotting Confirmation: Yes / No *
Laboratory:
Diagnosis made in: Hong Kong / overseas (specify )*
country:
Main route of transmission (please tick the right choice):
sex-heterosexual / homosexual / bisexual *
transfusion of blood – local / overseas (specify )*
date:
haemophilia
intravenous drug use
perinatal
other: (specify
not known

Section (B) Reporting AIDS

Is this an update of a previously HIV +case: Yes / No *
Date of diagnosis:
(DD/MM/YY)
AIDS defining illness(es):
1. clinical Dx / pathological Dx *
2. clinical Dx / pathological Dx *
3. clinical Dx / pathological Dx *
CD4 count per ul (if known): Date:
(DD/MM/YY)
Current status (please tick the right choice
an outpatient
an inpatient (Hospital: )
died (date: (DD/MM/YY) )
 Section
(C)
Name of medical practitioner: in private practice / public service *
Correspondence address:

Date: Tel no.:

* delete whichever inappropriate

ALL LIFORMATION WILL BE TREATED IN STRICT CONFIDENCE

161
Figure 1. Simplified serological profile of HIV infection

Figure 2. Route of transmission of reported HIV cases in Hong Kong (1984 – June 1995)

162
Figure 3. Route of transmission of reported HIV cases in Hong Kong (1984 – June 1995)

Figure 4. Estimated and projected annual AIDS cases in Hong Kong according to different HIV scenarios

163