CHAPTER
Acquired Immunodeciency
Syndrome
Kathleen A. Sweeney
THE AIDS EPIDEMIC AND TRANSMISSION
OF HIV INFECTION
Emergence of the AIDS Epidemic
Transmission of HIV Infection
PATHOPHYSIOLOGY AND CLINICAL COURSE
Molecular and Biologic Features of HIV
Classication and Phases of HIV Infection
HIV Infection and AIDS Case Denition Classication
Phases of HIV Infection
Clinical Course
Opportunistic Infections
Respiratory Manifestations
Gastrointestinal Manifestations
Nervous System Manifestations
Cancers and Malignancies
Wasting Syndrome
Metabolic and Morphologic Disorders
PREVENTION, DIAGNOSIS, AND TREATMENT
Prevention
Diagnostic Methods
Early Management
Treatment
Psychosocial Issues
HIV INFECTION IN PREGNANCY AND IN INFANTS
AND CHILDREN
T
he acquired immunodeficiency syndrome (AIDS)
is a disease caused by infection with the human
immunodeficiency virus (HIV) and is characterized
by profound immunosuppression with associated op-
portunistic infections, malignancies, wasting, and cen-
tral nervous system degeneration. Because the disease
affects an exceptionally high proportion of the popula-
tion throughout the world, it is often referred to as a
pandemic.1
22
The AIDS Epidemic and Transmission
of HIV Infection
After completing this section of the chapter, you should be able to
meet the following objectives:
Briey trace the history of the AIDS epidemic
State the virus responsible for AIDS and explain how it
differs from most other viruses
Describe the mechanisms of HIV transmission and relate
them to the need for public awareness and concern
regarding the spread of AIDS
As a national and global epidemic, the degree of mor-
bidity and mortality caused by HIV, as well as its impact on
health care resources and the economy, is tremendous
and unrelenting. At the end of 2002, it was estimated that
there were 42 million people worldwide living with HIV/
AIDS and that more than 25 million had died of the infec-
tion2 (Table 22-1). During the same year, 5 million people
were newly infected with the virus, and for the rst time,
women and young people 15 to 24 years of age accounted
for 50% of HIV infections. Because the reporting of cases
is not uniform throughout the world, many countries may
not be accurately represented in this number. Projections
for the next 10 years suggest that there will be 100 million
people infected with HIV.
Most of the new infections worldwide are in people
younger than 25 years of age who live in developing coun-
tries. Sub-Saharan Africa has been hardest hit by HIV.
There are 29.4 million people living with HIV in Africa,
with a reported 3.5 million new infections in 2002. There
are countries in Africa where more than 30% of the adults
are infected with HIV. Because of the large number of in-
fected people in Africa, the life expectancy is expected to
drop from 59 years to 45 years by 2005.3 Eastern Europe
and central Asia have the worlds fastest growing HIV pop-
ulation.2 In the United States, there had been more than
816,000 cases and more than 467,000 deaths from HIV at
the end of 2000, with racial and ethnic minorities being
disproportionately affected.3 Although blacks and Hispanics
427
428 UNIT V Inammation, Immunity, and Infection

TABLE 22-1 Estimated Number of Adults and Children Living With HIV/AIDS,
New Infections, and Deaths at the End of 2002

Living With Newly Infected Deaths

North America 980,000 45,000 15,000

Sub-Saharan Africa 29,400,000 3,500,000 2,400,000
Eastern Europe and Central Asia 1,200,000 250,000 25,000
East Asia and Pacic 1,200,000 270,000 45,000
South and South East Asia 6,000,000 700,000 440,000
Western Europe 570,000 30,000 8,000
Caribbean 440,000 60,000 42,000
Latin America 1,500,000 150,000 60,000
Australia and New Zealand 15,000 500 <100
Total 42 million 5 million 3.1 million

(Data from UNAIDS: AIDS epidemic updateDecember 2002.) Available online at

www.unaids.org/worldaidsday/2002/press/epiupdate.html.

represent a minority of the population in the United States,
they account for 55% of HIV infections.4
EMERGENCE OF THE AIDS EPIDEMIC
Compared with other human pathogens, HIV evolved very
recently. In 1981, clinicians in New York, San Francisco,
and Los Angeles recognized a new immunodeciency syn-
drome in homosexual men. Initially, the syndrome was
called GRIDS, for gay-related immunodeciency syn-
drome. By the end of 1981, there had been several hun-
dred cases reported, and the name was changed to acquired
immunodeciency syndrome, or AIDS.5 It soon became ap-
parent that this disease was not conned to one segment
of the population, but was also occurring in intravenous
drug users, hemophiliacs, blood transfusion recipients, in-
fants born to infected mothers, and high-risk heterosexu-
als. Studies of these diverse groups led to the conclusion
that AIDS was an infectious disease spread by blood, sexual
contact, and perinatally from mother to child.
An understanding of the virology of AIDS progressed
with amazing efficiency; within 3 years of the first cases
being recognized, the virus that causes AIDS had been
identified. The virus was initially known by various
names, including human T-cell lymphotropic virus type 3
(HTLV-III), lymphadenopathy-associated virus (LAV), and
AIDS-associated retrovirus (ARV).6 In 1986, the name human
immunodeciency virus became internationally accepted.7,8
not transmitted through casual contact. Several studies in-
volving more than 1000 uninfected, nonsexual household
contacts with persons with HIV infection (including sib-
lings, parents, and children) have shown no evidence of
casual transmission.9 HIV is not spread by mosquitoes or
other insect vectors.7 Transmission can occur when infected
blood, semen, or vaginal secretions from one person are
deposited onto a mucous membrane or into the blood-
stream of another person.
Sexual contact is the most frequent way that HIV is
transmitted. Worldwide, 75% to 85% of HIV infections are
transmitted through unprotected sex.10 HIV is present in
semen and vaginal uids. There is risk for transmitting
HIV when these uids come in contact with a part of the
body that lets them enter the bloodstream. This can in-
clude the vaginal mucosa, anal mucosa, and wounds or
sores on the skin.10 Contact with semen occurs during
vaginal and anal sexual intercourse, oral sex (i.e., fellatio),
and donor insemination. Exposure to vaginal or cervical
secretions occurs during vaginal intercourse and oral sex
(i.e., cunnilingus). Condoms are highly effective in pre-
venting the transmission of HIV. In most cities in the
United States, sexual transmission of HIV is primarily re-
lated to vaginal or anal intercourse. In the United States,
about 45% of HIV infections are among men who have sex
with men, and 11% are from heterosexual contact.3 In the
developing world, heterosexual transmission is the major
route of HIV infection.6

TRANSMISSION OF HIV INFECTION THE AIDS EPIDEMIC AND

TRANSMISSION OF HIV
HIV is a retrovirus that selectively attacks the CD4+ T lym-
phocytes, the immune cells responsible for orchestrating Acquired immunodeciency disease (AIDS) is caused by the
and coordinating the immune response to infection. As a human immunodeciency virus (HIV).
consequence, persons with HIV infection have a deteriorat-
HIV is transmitted through blood, semen, vaginal uids,
ing immune system, and thus are more susceptible to severe
and breast milk.
infections with ordinarily harmless organisms.
HIV is transmitted from one person to another through Persons with HIV are infectious even when asymptomatic.
sexual contact, blood-to-blood contact, or perinatally. It is

Because HIV is found in blood, the use of needles, sy-
ringes, and other drug injection paraphernalia is a direct
route for transmission. Of the reported cases of AIDS in
the United States, almost 25% occurred among persons
who injected drugs.3 HIV-infected injecting drug users
can pass the virus to their needle-sharing and sex part-
ners and, in the case of pregnant women, to their off-
spring.7 Although alcohol, cocaine, and other noninjected
drugs do not directly transmit infection, their use alters
perception of risk and reduces inhibitions about engag-
ing in behaviors that pose a high risk for transmitting
HIV infection.
Transfusions of whole blood, plasma, platelets, or blood
cells before 1985 resulted in the transmission of HIV. Since
1985, all blood donations in the United States have been
screened for HIV, and this is no longer a transmission risk.
The clotting factor used by persons with hemophilia is de-
rived from the pooled plasma of hundreds of donors. Be-
fore HIV testing of plasma donors was implemented in
1985, the virus was transmitted to persons with hemo-
philia through infusions of these clotting factors.7 Seventy
percent to 80% of hemophiliacs who were treated with
factor before 1985 became infected. Other blood products,
such as gamma globulin and hepatitis B immune globulin,
have not been implicated in the transmission of HIV.
Transmission from mother to infant is the most com-
mon way that children become infected with HIV. HIV
may be transmitted from infected women to their offspring
in utero, during labor and delivery, or through breast-
feeding.11 Ninety percent of infected children acquired the
virus from their mother. The risk for transmission of HIV
from mother to infant is approximately 25%, with esti-
mates ranging from 15% to 45% depending on what coun-
try they live in.12
Occupational HIV infection among health care work-
ers is uncommon. Through June 2000, the Centers for
Disease Control and Prevention (CDC) had received only
56 documented occupational HIV infections in the United
States.13 Fewer than 20 additional cases of occupational
infections have been reported from outside the United
States through the 1990s.14 Universal Blood and Body
Fluid Precautions should be used in encounters with all
patients in the health care setting because HIV status is
not always known. Occupational risk for infection of health
care workers most often is associated with percutaneous
inoculation (i.e., needle stick) of blood from a patient with
HIV. Transmission is associated with the size of the nee-
dle, amount of blood present, depth of the injury, type of
fluid contam-ination, stage of illness of the patient, and
viral load of the patient. The average risk for HIV infec-
tion from percutaneous exposure to HIV-infected blood is
about 0.3%, and about 0.9% after a mucous membrane
exposure.13
People with other sexually transmitted diseases (STDs)
are at increased risk for HIV infection. The risk for HIV
transmission is increased in the presence of genital ulcer-
ative STDs (i.e., syphilis, herpes simplex virus infection,
and chancroid) and nonulcerative STDs (i.e., gonorrhea,
chlamydial infection, and trichomoniasis). HIV increases
the duration and recurrence of STD lesions, treatment fail-
CHAPTER 22 Acquired Immunodeciency Syndrome 429
ures, and atypical presentation of genital ulcerative dis-
eases as a result of suppression of the immune system.
The HIV-infected person is infectious even when no
symptoms are present. The point at which an infected
person converts from being negative for the presence of
HIV antibodies in the blood to being positive is called
seroconversion. Seroconversion typically occurs within 1
to 3 months after exposure to HIV but can take up to
6 months.15 An HIV-infected person can occasionally trans-
mit the virus to others even before seroconversion. The
time after infection and before seroconversion is known as
the window period. During the window period, a persons
HIV antibody test will be negative. Rarely, infection can
occur from transfused blood that was screened for HIV anti-
body and found negative because the donor was recently
infected and still in the window period. Consequently, the
U.S. Food and Drug Administration (FDA) requires blood
collection centers to screen potential donors through in-
terviews designed to identify behaviors known to present
risk for HIV infection.
In summary, AIDS is an infectious disease of the immune sys-
tem caused by the HIV retrovirus that causes profound im-
munosuppression. First described in June 1981, the disease is
one of the leading causes of morbidity and mortality world-
wide. The severity of the clinical disease and the absence of a
cure or preventive vaccine have increased public awareness
and concern. In the most recent years, the greatest increase in
incidence of the disease has been in women and young
people 15 to 24 years of age.
HIV is transmitted from one person to another through
sexual contact, through blood-to-blood contact, or perina-
tally. Transmission occurs when the infected blood, semen,
or vaginal secretions from one person are deposited onto a
mucous membrane or into the bloodstream of another per-
son. The primary routes of transmission are through sexual
intercourse, through intravenous drug use, and from mother
to infant. Blood transfusions and other blood products con-
tinue to be routes of transmission in some underdeveloped
countries. Occupational exposure in health care settings ac-
counts for only a tiny percentage of HIV transmission. HIV in-
fection is not transmitted through casual contact or by insect
vectors. There is growing evidence of an association between
HIV infection and other STDs. Infected individuals can trans-
mit the virus to others before their own infections can be
detected by antibody tests.
Pathophysiology and Clinical Course
After completing this section of the chapter, you should be able to
meet the following objectives:
Describe the structure of HIV and trace its entry and
steps in replication within the CD4+ T lymphocyte
Describe the alterations in immune function that occur in
persons with AIDS
Describe the CDC HIV/AIDS classication system
430 UNIT V Inammation, Immunity, and Infection

Relate the altered immune function in persons with HIV
infection and AIDS to the development of opportunistic
infections, malignant tumors, nervous system manifesta-
tions, the wasting syndrome, and metabolic disorders
MOLECULAR AND BIOLOGIC
FEATURES OF HIV
HIV is a member of the lentivirus family of animal retro-
viruses.16,17 Lentiviruses, including feline immunodeciency
virus, simian immunodeciency virus, and the visna virus
of sheep, are capable of long-term latency and short-term
cytopathic effects. They can all produce slowly progressive
fatal diseases that include wasting syndromes and central
nervous system (CNS) degeneration. Two genetically dif-
ferent but antigenically related forms of HIV, HIV-1 and
HIV-2, have been isolated in people with AIDS. HIV-1 is the
type most associated with AIDS in the United States, Europe,
and Central Africa, whereas HIV-2 causes a similar disease
principally in West Africa. HIV-2 appears to be transmitted
in the same manner as HIV-1; it can also cause immuno-
deciency as evidenced by a reduction in the number of
CD4+ T cells and the development of AIDS. Although the
spectrum of disease for HIV-2 is similar to that of HIV-1,
it spreads more slowly and causes disease more slowly than
HIV-1. Specic tests are now available for HIV-2, and blood
collected for transfusion is routinely screened for HIV-2.
The ensuing discussion focuses on HIV-1.
The human immunodeciency virus infects a limited
number of cell types in the body, including a subset of
lymphocytes called CD4+ T lymphocytes (also known as
helper T cells or CD4+ T cells), macrophages, and dendritic
cells7 (see Chapter 19). The CD4+ T cells are necessary for
normal immune function. Among other functions, the
CD4+ T cell recognizes foreign antigens and helps activate
antibody-producing B lymphocytes.7 The CD4+ T cells also
orchestrate cell-mediated immunity, in which cytotoxic
CD8+ T cells and natural killer (NK) cells directly destroy
virus-infected cells, tubercular bacillus, and foreign antigens.
The phagocytic function of monocytes and macrophages is
also inuenced by CD4+ T cells.
Like other retroviruses, HIV carries its genetic informa-
tion in ribonucleic acid (RNA) rather than deoxyribonucleic
acid (DNA). The HIV virion is spherical in shape and con-
tains an electron-dense core surrounded by a lipid mem-
brane or envelope (Fig. 22-1). The virus core contains the

gp120 1 CD4+
Lipid binding site
membrane gp41

GP120

RNA
P17
2 3
Reverse
transcriptase
4
P 24 Viral
polyprotein
5

7
Reverse 8
transcriptase

FIGURE 22-1 Life cycle of the HIV-1: (1) Attachment of the HIV virus to CD4+ receptor; (2) internalization
and uncoating of the virus with viral RNA and reverse transcriptase; (3) reverse transcription, which pro-
duces a mirror image of the viral RNA and double-stranded DNA molecule; (4) integration of viral DNA
into host DNA using the integrase enzyme; (5) transcription of the inserted viral DNA to produce viral
messenger RNA; (6) translation of viral messenger RNA to create viral polyprotein; (7) cleavage of viral
polyprotein into individual viral proteins that make up the new virus; and (8) assembly and release of
the new virus from the host cell.

major capsid protein p24, two copies of the genomic RNA,
and three viral enzymes (protease, reverse transcriptase, and
integrase). Because p24 is the most readily detected antigen,
it is the target for the antibodies used in screening for HIV
infection. The viral core is surrounded by a matrix protein
called p17, which lies beneath the viral envelope. The viral
envelope is studded with two viral glycoproteins, gp120
and gp41, which are critical for the infection of cells.
Replication of HIV occurs in eight steps16,17 (see
Fig. 22-1). Each of these steps provides insights into the de-
velopment of methods used for preventing or treating the
infection. The rst step involves the binding of the virus to
the CD4+ T cell. Once HIV has entered the bloodstream, it
attaches to the surface of a CD4+ T cell by binding to a CD4
receptor that has a high afnity for HIV. However, binding
to the CD4 receptor is not sufcient for infection; the virus
must also bind with other surface molecules (chemokine
coreceptors) that bind the gp120 and gp41 envelope glyco-
proteins. This process is known as attachment. The second
step allows for the internalization of the virus. After attach-
ment, the viral envelope peptides fuse to the CD4+ T cell
membrane. Fusion results in an uncoating of the virus,
allowing the contents of the viral core (the two single
strands of viral RNA and the reverse transcriptase, integrase,
and protease enzymes) to enter the host cell. The chemokine
coreceptors are critical components of the HIV infection
process. It has recently been found that people with de-
fective coreceptors are more resistant to developing HIV,
despite repeated exposure.17
The third step consists of DNA synthesis. In order for the
HIV to reproduce, it must change its RNA into DNA. It does
this by using the reverse transcriptase enzyme. Reverse tran-
scriptase makes a copy of the viral RNA, and then in reverse
makes another mirror-image copy. The result is double-
stranded DNA that carries instructions for viral replication.
The fourth step is called integration. During integration, the
new DNA enters the nucleus of the CD4+ T cell and, with
the help of the enzyme integrase, is inserted into the cells
original DNA. The fth step involves transcription of the
double-stranded viral DNA to form a single-stranded mes-
PATHOPHYSIOLOGY OF AIDS
The HIV is a retrovirus that destroys the bodys immune
system by taking over and destroying CD4+ T cells.
In the process of taking over the CD4+ T cell, the virus at-
taches to receptors on the CD4+ cell, fuses to and enters the
cell, incorporates its RNA into the cells DNA, and then uses
the CD4+ cells DNA to reproduce large amounts of HIV,
which are released into the blood.
The three phases of HIV are primary HIV acute infection;
latency, during which there are no signs or symptoms of
disease; and overt AIDS, during which the CD4+ cell count
falls to low levels and signs of opportunistic infections and
other disease manifestations develop.
As the CD4+ T-cell count decreases, the body becomes sus-
ceptible to opportunistic infections.
CHAPTER 22 Acquired Immunodeciency Syndrome 431
senger RNA (mRNA) with the instructions for building new
viruses. Transcription involves activation of the T cell and
induction of host cell transcription factors. The sixth step
includes translation of mRNA. During translation, riboso-
mal RNA (rRNA) uses the instructions in the mRNA to cre-
ate a chain of proteins and enzymes called a polyprotein.
These polyproteins contain the components needed for
the next stages in the construction of new viruses. The sev-
enth step is called cleavage. During cleavage, the protease
enzyme cuts the polyprotein chain into the individual
proteins that will make up the new viruses. Finally, during
the eighth step, the proteins and viral RNA are assembled
into new HIV viruses and released from the CD4+ T cell.
HIV replication involves the killing of the CD4+ T cell
and the release of copies of the HIV into the bloodstream.
These viral particles, or virions, invade other CD4+ T cells,
allowing the infection to progress. Every day, millions of
infected CD4+ T cells are destroyed, releasing billions of
viral particles into the bloodstream; but each day, nearly
all the CD4+ T cells are replaced, and nearly all the viral
particles are destroyed. The problem is that over years, the
CD4+ cell count gradually decreases through this process,
and the number of viruses detected in the blood of persons
infected with HIV increases.18
Until the CD4+ cell count falls to a very low level, a per-
son infected with HIV can remain asymptomatic, although
active viral replication is still taking place and serologic
tests can identify antibodies to HIV.19 These antibodies, un-
fortunately, do not convey protection against the virus.
Although symptoms are not evident, the infection pro-
ceeds on a microbiologic level, including the invasion and
selective destruction of CD4+ T cells. The continual decline
of CD4+ T cells, which are pivotal cells in the immune re-
sponse, strips the person with HIV of protection against
common organisms and cancerous cells.18
CLASSIFICATION AND PHASES
OF HIV INFECTION
HIV Infection and AIDS Case
Denition Classication
Effective January 1, 1993, the CDC implemented a new clas-
sification system for HIV infection and a new AIDS case
definition for adolescents and adults that emphasizes the
clinical importance of the CD4+ cell count in the catego-
rization of HIV-related clinical conditions.20 The new clas-
sication system denes three categories that correspond to
CD4+ cell counts per microliter (L) of blood: category 1:
>500 cells/L, category 2: 200 to 499 cells/L, and category 3:
<200 cells/L (Fig. 22-2).
There also are three clinical categories. Clinical cate-
gory A includes persons who are asymptomatic or have
persistent generalized lymphadenopathy or symptoms of
primary HIV infection (i.e., acute seroconversion illness).
Clinical category B includes persons with symptoms of im-
mune deciency not serious enough to be AIDS dening.
Clinical category C includes AIDS-defining illnesses that
are listed in the AIDS surveillance case denition shown
in Chart 22-1. Each HIV-infected person has a CD4+ cell
count category and a clinical category. The combination
of these two categorizations, CD4+ cell count categories 1,
432 UNIT V Inammation, Immunity, and Infection

CD4+ cell count (u/L)

CHART 22-1
Category 1 Category 2 Category 3
Conditions Included in the 1993 AIDS
>500 cells 200 400 <200 cells
Surveillance Case Denition

Category A Candidiasis of bronchi, trachea, or lungs

AIDS defining clinical category

No defining criteria Candidiasis, esophageal

Cervical cancer, invasive*
Category B Coccidioidomycosis, disseminated or extrapulmonary
Symptoms not Cryptococcosis, extrapulmonary
severe enough Cryptosporidiosis, chronic intestinal
to be AIDS (>1 months duration)
defining Cytomegalovirus disease (other than liver, spleen, or
nodes)
Category C Cytomegalovirus retinitis (with loss of vision)
AIDS illness or
Encephalopathy, HIV-related
illnesses present
Herpes simplex: chronic ulcer(s) (>1 months duration)
or bronchitis, pneumonitis, or esophagitis
Equals AIDS defined
Histoplasmosis, disseminated or extrapulmonary
FIGURE 22-2 HIV classication for adolescents and adults. Isosporiasis, chronic intestinal (>1 months duration)
Kaposis sarcoma
Lymphoma, Burkitts (or equivalent term)
Lymphoma, immunoblastic (or equivalent term)
Lymphoma, primary, of brain
Mycobacterium avium-intracellulare complex or
2, and 3 and clinical categories A, B, and C, can guide clin-
M. kansasii, disseminated or extrapulmonary
ical and therapeutic decisions in the management of HIV Mycobacterium tuberculosis, any site (pulmonary* or
infection (see Fig. 22-2). According to the 1993 case de- extrapulmonary)
nition, persons in category 3 or category C are considered Mycobacterium, other species or unidentied species,
to have AIDS. disseminated or extrapulmonary
Pneumocystis carinii pneumonia
Phases of HIV Infection Pneumonia, recurrent*
The typical course of HIV is dened by three phases, which Progressive multifocal leukoencephalopathy
usually occur over a period of 8 to 12 years. The three phases Salmonella septicemia, recurrent
are the primary infection phase, chronic asymptomatic or Toxoplasmosis of brain
latency phase, and overt AIDS phase21 (Fig. 22-3). Wasting syndrome due to HIV
Many persons, when they are initially infected with
*Added to the 1993 expansion of the AIDS surveillance case
HIV, have an acute mononucleosis-like syndrome known
denition.
as primary infection. This acute phase may include fever, (Centers for Disease Control and Prevention. [1992]. 1993 Re-
fatigue, myalgias, sore throat, night sweats, gastrointestinal vised classication system for HIV infection and expanded
problems, lymphadenopathy, maculopapular rash, and surveillance case denition for AIDS among adolescents and
headache (Chart 22-2). Fever and rash are the symptoms adults. Morbidity and Mortality Weekly Report 41 [RR-17], 19)
most commonly associated with primary infection.22 Dur-
ing primary infection, there is an increase in viral replica-
tion, which leads to very high viral loads, sometimes greater
than 1,000,000 copies/mL, and a decrease in the CD4+ cell The primary phase is followed by a latent period dur-
count. The signs and symptoms of primary HIV infection ing which the person has no signs or symptoms of illness.
usually appear 2 to 4 weeks after exposure to HIV and last The median time of the latent period is about 10 years.
a few days to 2 weeks.21 After several weeks, the immune During this time, the CD4+ cell count falls gradually from
system acts to control viral replication and reduces the the normal range of 800 to 1000 cells/L to 200 cells/L or
viral load to a lower level, where it often remains for sev- lower.24 Lymphadenopathy develops in some persons with
eral years. HIV infection during this phase.24 Persistent generalized
People who are diagnosed with HIV while they are in lymphadenopathy usually is dened as lymph nodes that
the primary infection phase appear to have a unique op- are chronically swollen for more than 3 months in at least
portunity for treatment. It seems possible that if started two locations, not including the groin. The lymph nodes
early, treatment may reduce the number of long-living may be sore or visible externally.
HIV-infected cells (e.g., CD4+ memory cells).23 Early ther- The third phase, overt AIDS, occurs when a person
apy may also protect the functioning of HIV-infected has a CD4+ cell count of less than 200 cells/L or an AIDS-
CD4+ T cells and cytotoxic T cells. Finally, early treatment defining illness.21 Without antiretroviral therapy, this
can help maintain a homogeneous viral population that phase can lead to death within 2 to 3 years. The risk for
will be better controlled by antiretroviral therapy and the death and opportunistic infection increases significantly
immune system. when the CD4+ cell count reaches this level.
 CHAPTER 22 Acquired Immunodeciency Syndrome 433

Levels of viral
+ viral load
load and CD4
CD4 +
immune
T lymphocyte
response
count

HIV-1
exposure

24 weeks 810 years 23 years

Acute clinical syndrome Latency Overt AIDS
FIGURE 22-3 Viral load and CD4+ cell count during the phases of HIV.

CLINICAL COURSE Opportunistic infections involve common organisms that

The clinical course of HIV varies from person to person.
Most60% to 70%of those infected with HIV acquire
AIDS 10 to 11 years after infection. These people are the
typical progressors.21 Another 10% to 20% of those infected
progress rapidly. They acquire AIDS in less than 5 years
and are called rapid progressors. The final 5% to 15% are
slow progressors, who do not progress to AIDS for more than
15 years. There is a subset of slow progressors, called long-
term nonprogressors, who account for 1% of all HIV infec-
tions. These people have been infected for at least 8 years,
are antiretroviral nave, have high CD4+ cell counts, and
usually have very low viral loads (Fig. 22-4).
Opportunistic Infections
Opportunistic infections begin to occur as the immune
system becomes severely compromised. The number of
CD4+ T cells directly correlates with the risk for developing
opportunistic infections. Once the CD4+ cell count drops
below 200 cells/L, the risk for developing an opportunis-
tic infection is 33% after 1 year and 58% after 2 years.25
CHART 22-2
Signs and Symptoms of Acute HIV Infection
Fever
Fatigue
Rash
Headache
Lymphadenopathy
Pharyngitis
Arthralgia
Myalgia
Night sweats
Gastrointestinal problems
Aseptic meningitis
Oral or genital ulcers
normally do not produce infection unless there is im-
paired immune function. Although a person with AIDS
may live for many years after the rst serious illness, as the
immune system fails, these opportunistic illnesses become
progressively more severe and difcult to treat.
Most opportunistic infections can be categorized as
bacterial, fungal, protozoal, or viral. Bacterial opportunis-
tic infections include bacterial pneumonia, tuberculosis,
salmonellosis, and Mycobacterium aviumintracellulare
complex (MAC) infection. Fungal opportunistic infections
include candidiasis, coccidioidomycosis, cryptococcosis,
and histoplasmosis. Protozoal opportunistic infections
include cryptosporidiosis, isosporiasis, pneumocystiasis,
and toxoplasmosis. Viral infections include cytomegalo-
virus (CMV), herpes, and progressive multifocal leuko-
encephalopathy (PML).
In the United States, the most common opportunis-
tic infections are Pneumocystis carinii pneumonia (PCP),
oropharyngeal or esophageal candidiasis (thrush), CMV,
and infections caused by MAC.25
Respiratory Manifestations
The most common causes of respiratory disease in persons
with HIV infection are PCP and pulmonary tuberculo-
sis (TB).26 Other organisms that cause opportunistic pulmo-
nary infections in persons with AIDS include CMV, MAC,
Toxoplasma gondii, and Cryptococcus neoformans. Pneumonia
also may occur because of more common bacterial pulmo-
nary pathogens, including Streptococcus pneumoniae, Haemo-
philus inuenzae, and Legionella pneumophila. Some persons
may become infected with multiple organisms. Kaposis sar-
coma (to be discussed) also can occur in the lungs.
Pneumocystis carinii Pneumonia. P. carinii pneumonia
was the most common presenting manifestation of AIDS
during the rst decade of the epidemic. Since highly active
antiretroviral therapy (HAART) and prophylaxis for PCP
were instituted, the incidence has decreased.27 PCP still is
common in people who do not know their HIV status, in
those who choose not to treat their HIV, and in those with
434 UNIT V Inammation, Immunity, and Infection
FIGURE 22-4 Changes in viral load and CD4+ lymphocytes with regards to the different courses of HIV.
(Adapted from Rizzardi G.P., Pantaleo G. [1999]. The immunopathogenesis of HIV-1 infection. In Armstrong D.,
Cohen J. [Eds.], Infectious diseases. London: Harcourt)
poor access to health care. The best predictor of PCP is a
CD4+ cell count below 200 cell/L,28 and it is at this point
that prophylaxis with trimethoprim-sulfamethoxazole is
started.27 PCP is caused by P. carinii, an organism that is
common in soil, houses, and many other places in the
environment. In persons with healthy immune systems,
P. carinii does not cause infection or disease. In persons
with HIV, P. carinii can multiply quickly in the lungs and
cause pneumonia. As the disease progresses, the alveoli be-
come lled with foamy protein-rich uid causing impair-
ment of gas exchange (Fig. 22-5).
The symptoms of PCP may be acute or gradually pro-
gressive. Patients may present with complaints of a mild
cough, fever, shortness of breath, and weight loss. Physi-
cal examination may demonstrate only fever and tachyp-
nea, and breath sounds may be normal. The chest x-ray
lm may show interstitial inltrates, but in 5% of cases,
the x-ray may be negative.28 Diagnosis of PCP is made on
recognition of the organism in pulmonary secretions. This
can be done through examination of induced sputum,
bronchoalveolar lavage, occasionally bronchoscopy, and
rarely, lung biopsy.27
Mycobacterium tuberculosis. Tuberculosis is the leading
cause of death in people with HIV worldwide. More than
80,000 people are coinfected with HIV and TB in North
America and another 5 million in the rest of the world.29
TB cases in the United States decreased from the 1950s
until 1985; then, in 1986, the number of TB cases began to
increase (see Chapter 30). A number of factors contributed
to this increase, including changes in immigration pat-
terns and increased numbers of people living in group set-
tings like prisons, shelters, and nursing homes, but the
most profound factor is HIV infection. TB is often the rst
manifestation of HIV infection.
The lungs are the most common site of M. tuberculo-
sis infection, but extrapulmonary infection of the kidney,
bone marrow, and other organs also occurs in people
with HIV. Whether a person has pulmonary or extrapul-
monary TB, most patients present with fever, night sweats,
cough, and weight loss. Persons infected with M. tubercu-
losis (i.e., those with positive tuberculin skin tests) are
more likely to develop reactivated TB if they become in-
fected with HIV. Coinfected individuals are also more
likely to have a rapidly progressive form of TB. Equally
important, HIV-infected persons with TB coinfection
usually have an increase in viral load, which decreases
the success of TB therapy. They also have an increased
number of other opportunistic infections and an increased
mortality rate.
 CHAPTER 22 Acquired Immunodeciency Syndrome 435

A B

FIGURE 22-5 Pneumocystis carinii pneumonia. (A) The alveoli are lled with a foamy exudate, and the inter-
stitium is thickened and contains a chronic inammatory inltrate. (B) A centrifuged bronchoalveolar
lavage specimen impregnated with silver shows a cluster of Pneumocystis carinii cysts. (From Rubin E.,
Farber J.L. [1994]. Pathology [2nd ed.]. Philadelphia: J.B. Lippincott)

Since the late 1960s, most persons with TB have re-
sponded well to therapy. However, in 1991, there were
outbreaks of multidrug-resistant (MDR) TB.29 Many cases
of drug-resistant TB occur in HIV-infected persons. A sur-
vey of MDR TB in eight metropolitan areas in the United
States found that 38% of HIV-infected people with TB in
New York had MDR TB, as compared with 18% of HIV-
uninfected individuals with TB. Originally, mortality rates
from MDR TB among HIV-infected persons were high,
and the survival time was only approximately 2 months.
Now, because of earlier recognition and therapy, the sur-
vival time is approximately 7 months.
Gastrointestinal Manifestations
Diseases of the gastrointestinal tract are some of the most
frequent complications of HIV and AIDS. Esophageal can-
didiasis (thrush), CMV infection, and herpes simplex virus
infection are common opportunistic infections that cause
esophagitis in people with HIV.30 Persons experiencing
these infections usually complain of painful swallowing
or retrosternal pain. The clinical presentation can range
from asymptomatic to a complete inability to swallow
and dehydration. Endoscopy or barium esophagography
is required for definitive diagnosis.
Diarrhea or gastroenteritis is a common complaint
in persons with HIV. The most common protozoal in-
fection that causes diarrhea is Cryptosporidium parvum.
The clinical features of cryptosporidiosis can range from
mild diarrhea to severe, watery diarrhea with a loss of up
to several liters of water per day. The most severe form
usually occurs in persons with a CD4+ cell count of less
than 50 cells/L, and also can include malabsorption,
electrolyte disturbances, dehydration, and weight loss.21
Other organisms that cause gastroenteritis and diarrhea
are Salmonella, Shigella, and Giardia species, CMV, Clostrid-
ium difficile, Escherichia coli, and microsporida.30 These
organisms are identied by examination of stool cultures
or endoscopy.
Nervous System Manifestations
Human immunodeciency virus infection, particularly in
its late stages of severe immunocompromise, leaves the
nervous system vulnerable to an array of neurologic dis-
orders, including AIDS dementia complex (ADC), toxoplas-
mosis, and PML. These disorders can affect the peripheral
or central nervous system (CNS) and contribute to the mor-
bidity and mortality of persons with HIV.
AIDS Dementia Complex. AIDS dementia complex, or HIV-
associated dementia, is a syndrome of cognitive and motor
dysfunction.31 ADC is caused by HIV itself, rather than an
opportunistic infection, and usually is a late complication
of HIV. The clinical features of ADC are impairment of at-
tention and concentration, slowing of mental speed and
agility, slowing of motor speed, and apathetic behavior.
The diagnosis of ADC can be based on these clinical find-
ings. Treatment of ADC consists of HAART therapy to
decrease symptoms, but there is no cure.
Toxoplasmosis. Toxoplasmosis is a common opportunis-
tic infection in persons with AIDS. The organism responsi-
ble, T. gondii, is a parasite that most often affects the CNS.32
Toxoplasmosis usually is a reactivation of a latent T. gondii
infection that has been dormant in the CNS. The typical
presentation includes fever, headaches, and neurologic
dysfunction, including confusion and lethargy, visual
disturbances, and seizures. Computed tomography scans or
magnetic resonance imaging (MRI) should be performed im-
mediately to detect the presence of neurologic lesions. Pro-
phylactic treatment with trimethoprim-sulfamethoxazole
is effective against T. gondii when the CD4+ cell count
falls below 200 cells/L. Since the use of trimethoprim-
sulfamethoxazole and HAART was put into practice, the
incidence of toxoplasmosis has decreased.31
Progressive Multifocal Leukoencephalopathy. Progressive
multifocal leukoencephalopathy is a demyelinating disease of
436 UNIT V Inammation, Immunity, and Infection

the white matter of the brain caused by the JC virus, a DNA

papovavirus that attacks the oligodendrocytes.31 PML ad-
vances slowly, and it can be weeks to months before the
patient seeks medical care. PML is characterized by pro-
gressive limb weakness, sensory loss, difculty controlling
the digits, visual disturbances, subtle alterations in mental
status,33 hemiparesis, ataxia, diplopia, and seizures.34 The
mortality rate is high, and the average survival time is 2 to
4 months. Diagnosis is based on clinical ndings and an
MRI, and conrmed by the presence of the JC virus.33 There
is no proven cure for PML, but improvement can occur
after starting HAART.34

Cancers and Malignancies

Persons with AIDS have a high incidence of certain malig-
nancies, especially Kaposis sarcoma (KS), non-Hodgkins
lymphoma, and noninvasive cervical carcinoma. It has
been reported that KS or lymphoma is likely to develop in
as many as 30% to 40% of people with HIV.35 The in-
creased incidence of malignancies probably is a function
of impaired cell-mediated immunity.
Kaposis Sarcoma. Kaposis sarcoma is a malignancy of the
endothelial cells that line small blood vessels.36 An oppor-
tunistic cancer, KS occurs in immunosuppressed persons
(e.g., transplant recipients or persons with AIDS). KS was
one of the rst opportunistic cancers associated with AIDS
and remains the most frequent malignancy related to
HIV. It is 2000 times more common in people infected with
HIV than in the rest of the population.35 Before 1981, most
cases of KS were found in North America among elderly
men of Mediterranean or Eastern European Jewish descent
and in Africa among young black adults and children.37
There is evidence linking KS to a herpesvirus (herpes-
virus-8, also called KS-associated herpes virus [KSHV]).37
More than 95% of KS lesions, regardless of the source or
clinical subtype, have reportedly been found to be infected
with KSHV. The virus is readily transmitted through ho-
mosexual and heterosexual activities. Maternalinfant
transmission also occurs. The virus has been detected in
saliva from infected persons, and other modes of trans-
mission are suspected.
The lesions of KS can be found on the skin and in the
oral cavity, gastrointestinal tract, and lungs. More than
50% of people with skin lesions also have gastrointestinal
lesions. The disease usually begins as one or more macules,
papules, or violet skin lesions that enlarge and become
darker (Fig. 22-6). They may enlarge to form raised plaques
or tumors. These irregularly shaped tumors can be from one
eighth of an inch to silver dollar size. Tumor nodules fre-
quently are located on the trunk, neck, and head, especially
the tip of the nose. They usually are painless in the early
stages, but discomfort may develop as the tumor develops.
Invasion of internal organs, including the lungs, gastroin-
testinal tract, and lymphatic system, commonly occurs.
Gastrointestinal tract KS is often asymptomatic but can
cause pain, bleeding, or obstruction.35 Pulmonary KS usu-
ally is a late development of the disease and causes dyspnea,
cough, and hemoptysis.36 The tumors may obstruct organ
function or rupture and cause internal bleeding. The pro-
gression of KS may be slow or rapid.
FIGURE 22-6 Disseminated Kaposis sarcoma. Multiple red to brown
papules distributed along the skin lines in a man with AIDS. (Hall
J.C. [2000]. Sauers manual of skin [8th ed., p. 197]. Philadelphia: Lip-
pincott Williams & Wilkins)
A presumptive diagnosis of KS usually is made based on
visual identication of red or violet skin or oral lesions.35
Biopsy of at least one lesion must be done to establish the
diagnosis and to distinguish the KS from other skin lesions
that may resemble it. Diagnosis of gastrointestinal or pul-
monary KS is more difcult because endoscopy and bron-
choscopy are needed for diagnosis. Effective HAART, local
therapy with liquid nitrogen or vinblastine, chemotherapy,
radiation, and interferon injections are the most common
therapies.36 These therapies are only palliative and are not a
cure. However, with evidence that links KS to a herpesvirus,
there is hope that effective therapies will be developed for
preventing KS in persons at risk.37
Non-Hodgkins Lymphoma. Non-Hodgkins lymphoma
(see Chapter 17) develops in 3% to 4% of people with HIV
infection.35 The clinical features are fever, night sweats, and
weight loss. Because the manifestations of non-Hodgkins
lymphoma are similar to those of other opportunistic
infections, diagnosis often is difficult. Diagnosis can be
made by biopsy of the affected tissue. Treatment includes
aggressive combination chemotherapy that includes intra-
thecal chemotherapy. The prognosis for those with non-
Hodgkins lymphoma is poor, with survival ranging from
4 to 20 months.
Noninvasive Cervical Carcinoma. Women with HIV in-
fection experience a higher incidence of cervical dysplasia
than nonHIV-infected women.38,39 These lesions are usu-
ally a slowly developing precursor to cervical carcinoma
and progress rapidly in women with HIV infection. Cervi-
cal carcinoma results from infection with human papillo-
mavirus.39 In addition to the rapid progression from mild
dysplasia to carcinoma in situ, women with HIV infection
may be less responsive to standard treatments and have a

poorer prognosis than uninfected women.38 Occurrence of
cervical dysplasia is detected by Papanicolaou smear and
cervical colposcopy.
Wasting Syndrome
In 1997, wasting became an AIDS-dening illness. The syn-
drome is common in persons with HIV infection or AIDS.
Wasting is characterized by involuntary weight loss of at
least 10% of baseline body weight in the presence of diar-
rhea, more than two stools per day, or chronic weakness and
a fever.40 This diagnosis is made when no other opportu-
nistic infections or neoplasms can be identied as causing
these symptoms. Factors that contribute to wasting are ano-
rexia, metabolic abnormalities, endocrine dysfunction, mal-
absorption, and cytokine dysregulation. Treatment for wast-
ing includes nutritional interventions like oral supplements
or enteral or parenteral nutrition. There also are numerous
pharmacologic agents used to treat wasting, including
appetite stimulants, cannabinoids, and megestrol acetate.
Metabolic and Morphologic Disorders
A wide range of metabolic and morphologic disorders is
associated with HIV infection, including lipodystrophy
and mitochondrial disorders, hypercholesterolemia, hyper-
triglyceridemia, insulin resistance, and impaired glucose
tolerance. Metabolic complications among people with
HIV on HAART have been increasing during the past ve
years.41 Diabetes is now seen in 0.5% to 4.4% of people on
HAART. Insulin resistance is seen in as many as 55% of pa-
tients receiving protease inhibitors (PIs). It is still not
known why insulin resistance occurs in people with HIV.
Treatment of insulin resistance is the same as for people
without HIV: a healthy balanced diet, exercise, and weight
loss if needed (see Chapter 43).
Lipid abnormalities such as increases in triglycerides
and cholesterol are also becoming more common in per-
sons with HIV. Most protease inhibitors (PIs) have been
shown to increase LDL and triglycerides.41 Before beginning
antiretroviral therapy, a fasting lipid panel should be
drawn, then repeated in 3 to 6 months, and then repeated
yearly. Currently, treatment of these lipid abnormalities
includes use of the dietary guidelines recommended by the
National Cholesterol Education Program (NCEP).42 There is
evidence to indicate that switching from a PI-containing
to a nonPI-containing regimen is beneficial. The statins
(e.g., atorvastatin, fluvastatin, pravastatin, simvastatin,
discussed in Chapter 24) are the recommended medication
to manage hypercholesterolemia, although caution must
be used because there can be drug-metabolizing interactions
between the PIs, nonnucleoside reverse transcriptase in-
hibitors (NNRTIs), and statins. Because increased triglyc-
erides can lead to pancreatitis, the bric acid derivatives
(e.g., gembrozil and fenobrate) may be prescribed as a
means of decreasing triglyceride levels.
Lipodystrophy. A metabolic disorder called lipodystrophy
is one of the newest group of problems for those infected
with HIV. Lipodystrophy related to HIV includes symptoms
that fall into two categories: changes in body appearance
and metabolic changes.43 The alterations in body appear-
ance are an increase in abdominal girth, buffalo hump
CHAPTER 22 Acquired Immunodeciency Syndrome 437
development (abnormal distribution of fat in the supra-
clavicular area), wasting of fat from the face and extrem-
ities, and breast enlargement in men and women. The
metabolic changes include elevated serum cholesterol and
triglyceride levels and insulin resistance. Originally attrib-
uted to the use of protease inhibitors, the pathogenesis of
lipodystrophy is still not understood. It may be due to pro-
tease inhibitor therapy or nucleoside reverse transcriptase
inhibitor therapy, or may arise simply because people are
living longer with HIV.
There is no case definition for lipodystrophy; thus,
diagnosis is based on patient complaints, clinical monitor-
ing of triglycerides and cholesterol, and body shape.43
Recently, the European Evaluation Agency, which is the
European equivalent of the FDA, began a study to come
up with a case denition of lipodystrophy.41 They isolated
10 factors that dene lipodystrophy: being female, being
older than age 40, having HIV for more than 4 years, reach-
ing CDC stage C AIDS classication, and having a wide
anion gap, low HDL levels, increased waist-to-hip ratio,
high visceral adipose tissue (VAT)tosubcutaneous adipose
tissue (SAT) ratio, increased trunk-to-limb fat ratio, and de-
creased percentage of leg fat.
There is no consensus on the best treatment for lipo-
dystrophy. Preliminary studies suggest that recombinant
human growth hormone (RHGH) decreases VAT and SAT,
although its use has been associated with a high frequency
of adverse affects.41 Metformin, an oral antidiabetic drug,
has also been used, and patients have experienced in-
creased glucose tolerance, a decrease in weight, and a de-
crease in waist circumference. Some authorities recommend
switching to a nonprotease inhibitorbased HAART regi-
men. The problem with this is that although triglycerides
and cholesterol decrease,43 and there is some resolution to
the fat redistribution, viral load can increase and become
detectable.44 Liposuction has been used with some success
for patients with breast enlargement.43 Many clinicians ini-
tiate lipid-lowering therapy.45 The long-term consequences
of these metabolic changes need to be carefully evaluated,
and management guidelines need to be developed.
Mitochondrial Disorders. The mitochondria control many
of the oxidative chemical reactions that release energy from
glucose and other organic molecules.43 The mitochondria
transform this newly released energy into adenosine tri-
phosphate (ATP), which cells use as an energy source. In
the absence of normal mitochondrial function, cells revert
to anaerobic metabolism with generation of lactic acid. The
mitochondrial disorders seen in persons with HIV are caused
by antiretroviral therapy, in particular, nucleoside reverse
transcriptase inhibitors (NRTIs). Patients often present with
nonspecic gastrointestinal symptoms, including nausea,
vomiting, and abdominal pain. On examination, they can
have hepatomegaly with normal liver function test results.
The only laboratory abnormality may be lactic acidosis.
Mitochondrial dysfunction is the most feared complica-
tion of antiretroviral therapy. This fear is due to the con-
ditions unpredictability, its fatality in half of presenting
patients, the nonspecic presenting symptoms, and the
prevalence of elevated lactate levels in 8% to 22% of pa-
tients who are asymptomatic.46
438 UNIT V Inammation, Immunity, and Infection
In summary, HIV is a retrovirus that infects the bodys CD4+
T cells and macrophages. The integration of viral RNA into the
DNA of infected cells allows the virus to replicate, thereby in-
fecting and eventually producing a profound loss of CD4+ cells
from the peripheral blood.
The course of infection occurs in three phases: an acute
mononucleosis-like infection that occurs shortly after infection,
a latent phase that may last years, and an overt AIDS phase
that occurs when the CD4+ cell count falls to 200 cell u/L or
less. The AIDS phase is marked by the onset of opportunistic
infections and cancers. These opportunistic pathologies can af-
fect the respiratory, gastrointestinal, nervous, and other body
systems causing conditions such as pneumonia, esophagitis,
diarrhea, gastroenteritis, tumors, wasting syndrome, dementia,
seizures, motor decits, and metabolic disorders.
Prevention, Diagnosis, and Treatment
After completing this section of the chapter, you should be able to
meet the following objectives:
Discuss the transmission of HIV
Describe preventive strategies to decrease the
transmission of HIV
Explain the possible signicance of a positive antibody
test for HIV infection
Differentiate between the enzyme immunoassay
(enzyme-linked immunosorbent assay) and Western blot
antibody detection tests for HIV infection
Describe the methods used in the early management of
HIV infection
Compare the actions of the reverse transcriptase
inhibitors (e.g., nucleoside reverse transcriptase inhibitors,
nucleotide analog reverse transcriptase inhibitors),
nonnucleoside reverse transcriptase inhibitors, protease
inhibitors, and fusion inhibitors in terms of controlling
HIV replication
Enumerate some of the psychosocial issues associated
with HIV/AIDS
Since the rst description of AIDS, considerable strides
have been made in understanding the pathophysiology of
the disease. The virus and its mechanism of action, HIV
antibody screening tests, and some treatment methods
were discovered within a few years after the recognition of
the rst cases. Further progress in understanding the patho-
physiology of AIDS and the development of more power-
ful treatments continues to be made.
PREVENTION
Because there is no cure for HIV or AIDS, adopting risk-free
or low-risk behavior is the best protection against the dis-
ease. Abstinence or long-term, mutually monogamous sex-
ual relationships between two uninfected partners are the
best ways to avoid HIV infection and other STDs. Correct
and consistent use of latex condoms can provide protection
from HIV by not allowing contact with semen or vaginal se-
cretions during intercourse.10 Natural or lambskin condoms
do not provide the same protection from HIV as latex be-
cause of the larger pores in the material. Only water-based
lubricants should be used with condoms; petroleum (oil-
based) products weaken the structure of the latex.
Injection of drugs provides another opportunity for
HIV transmission. Avoiding recreational drug use and par-
ticularly avoiding the practice of using syringes that may
have been used by another person are important to HIV
prevention. Medical and public health authorities recom-
mend that persons who inject drugs use a new sterile sy-
ringe for each injection or, if this is not possible, clean their
syringes thoroughly with a household bleach mixture.
Other substances that alter inhibitions can lead to risky
sexual behavior and increase the risk for exposure to HIV.
For example, smoking cocaine (i.e., crack) heightens the
perception of sexual arousal, and this can inuence the
user to practice unsafe sexual behavior.47 The addictive na-
ture of many recreational drugs can lead to an increase in
the frequency of unsafe sexual behavior and the number of
partners as the user engages in sex exchanged for money
or drugs. Persons concerned about their risk should be
encouraged to get information and counseling and to be
tested to nd out their infection status.
Public health programs in the United States have been
profoundly affected by the HIV epidemic. Although stan-
dard methods for disease intervention and statistical analy-
sis are applied to HIV, public health programs have become
more responsive to community concerns, condentiality,
and long-term follow-up of clients as a direct result of the
HIV epidemic. Testing for HIV antibodies and counseling
have become widely available in the United States. When-
ever HIV testing is performed, pretest and posttest counsel-
ing should be offered. HIV prevention counseling should be
culturally competent, sensitive to issues of sexual identity,
developmentally appropriate, and linguistically relevant.12
The essential elements of any HIV prevention or coun-
seling interaction include a personalized risk assessment
and prevention plan.48 Education and behavioral interven-
tion continue to be the mainstays of HIV prevention pro-
grams. Individual risk assessment and education regarding
HIV transmission and possible prevention techniques or
skills are delivered to persons in clinical settings and to
those at high risk for infection in community settings.
Community-wide education is provided in schools, in the
workplace, and in the media. Training for professionals can
have an impact on the spread of HIV and is an important
element of prevention. The constant addition of new in-
formation on HIV makes prevention an ever-changing and
challenging endeavor.
DIAGNOSTIC METHODS
The diagnostic methods used for HIV infection include
laboratory methods to determine infection and clinical
methods to evaluate the progression of the disease. The
most accurate and inexpensive method for identifying
HIV is the HIV antibody test. The rst commercial assays
for HIV were introduced in 1985 to screen donated blood.

Since then, use of antibody detection tests has been
expanded to include evaluating persons at increased risk for
HIV infection. The HIV antibody test procedure consists of
screening with an enzyme immunoassay (EIA), also known as
enzyme-linked immunosorbent assay (ELISA), followed by a
conrmatory test, the Western blot assay, which is per-
formed if the EIA is positive.49 EIA tests are used rst because
they are less expensive and are quicker to perform. In light
of the psychosocial issues related to HIV and AIDS, sensi-
tivity and condentiality must be maintained whenever
testing is implemented. Counseling before and after testing
to allay fears, provide accurate information, ensure appro-
priate follow-up testing, and provide referral to needed
medical and psychosocial services is essential.
The EIA detects antibodies produced in response to HIV
infection.19 In an EIA test, when blood is added, antibodies
to HIV bind to HIV antigens. The antigenantibody com-
plex is then detected using an antihuman immunoglobu-
lin G (IgG) antibody conjugated to an enzyme like alkaline
phosphatase. A substrate is then added from which the en-
zyme produces a color reaction. Color development, indi-
cating the amount of HIV antibodies found, is measured.
The test is considered reactive, or positive, if color is pro-
duced, and negative, or nonreactive, if there is no color. EIA
tests have high false-positive rates; thus, samples that are re-
peatedly reactive are tested by a conrmatory test such as
the Western blot.
The Western blot test is more specic than the EIA, and
in the case of a false-positive EIA test result, the Western
blot test can identify the person as uninfected. The Western
blot is a more sensitive assay that looks for the presence of
antibodies to specic viral antigens.19 For the test, HIV anti-
gens are separated by electrophoresis based on their weight,
and then transferred to nitrocellulose paper and arranged in
strips, with larger proteins at the top and smaller proteins at
the bottom. The serum sample is then added. If HIV anti-
bodies are present, they bind with the specic viral antigen
on the paper. An enzyme and substrate then are added to
produce a color reaction as in the EIA test. If there are no
colored bands present, the test is negative. A test is positive
when certain combinations of bands are present. A test can
be indeterminate if there are bands present but they do not
meet the criteria for a positive test result. An indeterminate
or false-positive test result can occur during the window pe-
riod before seroconversion. When a serum antibody test re-
sult is reactive or borderline by EIA and positive by Western
blot, the person is considered to be infected with HIV.
When an EIA is reactive, and the Western blot is negative,
the person in not infected with HIV. Both tests are impor-
tant because, in some situations, misinformation can be
generated by EIA testing alone because there are many situ-
ations that can produce a false-positive (Chart 22-3) or a
false-negative ELISA result. The Western blot test therefore
is essential to determine which persons with positive EIA
tests are truly infected.
Millions of HIV antibody tests are performed in the
United States each year. New technology has led to new
forms of testing, like the oral test, home testing kits, and the
new rapid blood test. Oral uids contain antibodies to HIV.
In the late 1990s, the FDA approved the OraSure test.19
CHAPTER 22 Acquired Immunodeciency Syndrome 439
CHART 22-3
Causes of False-Positive or False-Negative
HIV ELISA Test Results
False-Positive Results
Hematologic malignant disorders (e.g., malignant
melanoma)
DNA viral infections (e.g., infectious mononucleosis
[Epstein-Barr virus])
Autoimmune disorders
Primary biliary cirrhosis
Immunizations (inuenza, hepatitis)
Passive transfer of HIV antibodies (mother to infant)
Antibodies to class II leukocytes
Chronic renal failure/renal transplant
Stevens-Johnson syndrome
Positive rapid plasma reagin test
False-Negative Results
Window period after infection
Immunosuppression therapy
Replacement transfusion
B-cell dysfunction
Bone marrow transplant
Contamination of specimen with starch powder from
gloves
Use of kits that detect primary antibody to the p24
viral core protein
The OraSure uses a cotton swab, which is inserted into the
mouth for 2 minutes, placed in a transport container with
preservative, and then sent to a laboratory for EIA and West-
ern blot testing. Home HIV testing kits can be bought over
the counter. The kits, approved by the FDA, allow persons
to collect their own blood sample through a nger-stick
process, mail the specimen to a laboratory for EIA and
confirmatory Western Blot tests, and receive results by
telephone in 3 to 7 days. In November 2002, the FDA ap-
proved the Ora Quick Rapid HIV-1 Antibody Test.50 The
Ora Quick uses a whole blood specimen from a nger stick
and can provide results in about 20 minutes. Reactive, or
positive, test results require confirmation using Western
blot testing. A person with a reactive result needs to be
told that the preliminary test was positive, but they need
a confirmatory test. The use of a rapid test should facili-
tate people receiving the results of their HIV test more
regularly because they do not need to return for their test
results 2 weeks later.
Polymerase chain reaction (PCR) is a technique for de-
tecting HIV DNA (see Chapter 18). PCR detects the pres-
ence of the virus rather than the antibody to the virus,
which the EIA and Western blot tests detect.51 PCR is use-
ful in diagnosing HIV infection in infants born to infected
mothers because these infants have their mothers HIV
antibody regardless of whether or not the infants are in-
fected. Because the amount of viral DNA in the HIV-
infected cell is small compared with the amount of human
DNA, direct detection of viral genetic material is difcult.
440 UNIT V Inammation, Immunity, and Infection
PCR is a method for amplifying the viral DNA up to 1 mil-
lion times or more to increase the probability of detection.
EARLY MANAGEMENT
The management of HIV infection has changed dramati-
cally since the mid-1990s. This change is due to a better
understanding of the pathogenesis of HIV, the emergence of
viral load testing, and the increased number of medications
available to ght the virus. After HIV infection is conrmed,
a baseline evaluation should be done.52 This evaluation
should include a complete history and physical examina-
tion and baseline laboratory tests. Routine follow-up care of
a stable, asymptomatic HIV-infected patient should include
a history and physical examination along with CD4+ cell
count and viral load testing every 3 to 4 months. Persons
who are symptomatic may need to be seen more frequently.
Therapeutic interventions are determined by the level
of disease activity based on the viral load, the degree of im-
munodeciency based on the CD4+ cell count, and the ap-
pearance of specic opportunistic infections. The current
guidelines released July 14, 2003 recommend that anti-
retroviral therapy be initiated when a persons CD4+ cell
count is less than 350 cells/l or the viral load is greater
than 55,000 copies/mL.53 As HIV progresses, prophylaxis
and treatment of opportunistic infections becomes very
important.52 Prophylaxis is different for every opportunis-
tic infection and depends on the persons CD4+ cell count.
Early recognition of HIV is becoming more common, and
medical intervention in the early stages may delay life-
threatening symptoms and slow the spread of disease.
Because of frequent advances in the management of
HIV infection, primary care providers must be prepared to
update their knowledge of diagnosis, testing, evaluation,
and medical intervention. The CDC, the Department of
Health and Human Services, and the U.S. Public Health
Service regularly issue guidelines to assist clinicians in car-
ing for persons with HIV disease.
TREATMENT
There is no cure for HIV. The medications that are currently
available to treat HIV decrease the amount of HIV in the
body, but they do not get rid of the HIV virus. The treat-
ment of HIV is one of the most rapidly evolving elds in
medicine. Because different drugs act on different stages of
the replication cycle, optimal treatment includes a combi-
nation of at least three drugs, often referred to as HAART.54
The goal of HAART is a sustained suppression of HIV repli-
cation, resulting in an undetectable viral load and an in-
creasing CD4+ cell count. In general, antiviral therapies are
prescribed to slow the progression to AIDS and improve the
overall survival time of persons with HIV infection.
The rst drug that was approved by the FDA for the
treatment of HIV was zidovudine, which came out in
1987.54 Since then, an increasing number of therapeutics
have been approved by the FDA for treatment of HIV in-
fection. There currently are ve different types of HIV an-
tiretroviral medications: nucleoside reverse transcriptase
inhibitors; nucleotide analog reverse transcriptase inhibi-
tors; nonnucleoside reverse transcriptase inhibitors; pro-
tease inhibitors; and the newest class, fusion inhibitors
(Table 22-2). Each type of agent attempts to interrupt viral
replication at a different point.
Reverse transcriptase inhibitors inhibit HIV replication
by acting on the enzyme reverse transcriptase.55 Three
types of HIV medications work on this enzyme: nucleo-
side reverse transcriptase inhibitors, nucleotide analog
reverse transcriptase inhibitors, and nonnucleoside reverse
transcriptase inhibitors. Nucleoside reverse transcriptase in-
hibitors and nucleotide analog reverse transcriptase inhibitors
act by blocking the elongation of the DNA chain by stop-
ping more nucleosides from being added. Nonnucleoside re-
verse transcriptase inhibitors work by binding to the reverse
transcriptase enzyme so that it cannot copy the viruss RNA
into DNA (see Fig. 22-1).
Protease inhibitors bind to the protease enzyme and in-
hibit its action.52 This inhibition prevents the cleavage of
the polyprotein chain into individual proteins, which
would be used to construct the new virus. Because the in-
formation inside the nucleus is not put together properly,
the new viruses that are released into the body are imma-
ture and noninfectious (see Fig. 22-1).
The newest class of antiretroviral therapy consists of
the fusion inhibitors. These prevent HIV from fusing with the
CD4+ cell, thus blocking the HIV from inserting its genetic
information into the CD4+ T cell56 (see Fig. 22-1). The FDA
approved the rst of this class in March 2003. It is a sub-
cutaneous injection given twice daily.
Many other HIV medications are currently under in-
vestigation, including two new classes of drugsentry
inhibitors and integrase inhibitors. Entry inhibitors, which
include fusion inhibitors as well as receptor blockers, block
the receptors on the CD4+ T cells so that the HIV cannot
attach to the CD4+ T cell.57 Integrase inhibitors prevent the
HIV DNA from being integrated into the host genome.
work during the integration phase of the life cycle when
the new genetic pieces are being brought together and
they disrupt this process.
Finding a vaccine for HIV is also being investigated.
There are currently two types of vaccines being exam-
ined.58 First, there is a vaccine that would prevent infec-
tion. This vaccine would be given to someone who is HIV
negative, with the goal of preventing infection if exposed
to HIV. These vaccines have focused on stimulating the
development of neutralizing antibodies to prevent HIV in-
fection. The second type of vaccine would be used in peo-
ple who are already infected with HIV. The goal of these
vaccines would be to better control the HIV viremia by
lowering the viral load set point, changing the viral load
trajectories, or preserving immune function for longer pe-
riods of time. These vaccines have focused on boosting the
bodys cellular immune responses and preparing the cyto-
toxic t-cells for lysis of HIV infected cells.
Opportunistic infections occur as a consequence of
immunodeficiency, which is caused by the progressive
loss of CD4+ T cells. Drugs and vaccines commonly are
used for the prevention and treatment of opportunistic
infections and conditions, including PCP, toxoplasma,
MAC,59 candidal, CMV, inuenza, hepatitis B, and S. pneu-
 CHAPTER 22 Acquired Immunodeciency Syndrome 441

TABLE 22-2 Antiviral Medications Used in the Treatment of HIV Infection

Medication (Generic Name and Initials)

by Classication Medication (Trade Name) Dosing Schedule

Nucleoside Reverse Inhibitors

Zidovudine (AZT) Retrovir Twice daily
Didanosine (ddl) Videx Twice daily
Didanosine (ddl) enteric coated Videx EC Once daily
Lamivudine (3TC) Epivir Twice daily
Stavudine (d4T) Zerit Twice daily
Abacavir Ziagen Twice daily
Zalcitabine (ddC) Hivid Every 8 hours
AZT and 3TC Combivir Twice daily
AZT, 3TC, and abacavir Trizir Twice daily
Emtricitabine (FTC) Emtiriva Once daily
Nucleoside Analog Reverse Transcriptase Inhibitors
Tenofovir (TNV) Viread Once daily
Nonnucleoside Reverse Transcriptase Inhibitors
Nevirapine (NVP) Viramune Twice daily
Efavirenz (EFV) Sustiva Once daily
Delavirdine (DLV) Rescriptor Three times
daily
Protease Inhibitors
Saquinavir (SAQ) Invirase, Fortovase Every 8 hours
Ritonavir (RTV) Novir Every 12 hours
Indinavir (IDV) Crixivan Every 8 hours
Nelnavir (NLF) Viracept Every 12 hours
Amprenavir (APV) Agenerase Every 12 hours
Lopinavir/ritonavir Kaletra Every 12 hours
Atazanavir Reyataz Once a day
Fusion Inhibitors
Enfuvirtide (T-20) Fuzeon Every 12 hours

moniae infections.60,61 Prophylactic medications are used
once an individuals CD4+ cell count has dropped below
a certain level that indicates his or her immune system is
no longer able to ght off opportunistic infections.
Persons with HIV should be advised to avoid infec-
tions as much as possible and seek evaluation promptly
when they occur. Immunization is important because per-
sons infected with HIV are at risk for contracting other in-
fectious diseases. Some of these diseases can be avoided by
vaccination while the immune systems responsiveness is
relatively intact.62 Persons with asymptomatic HIV infec-
tion should be vaccinated against measles, mumps, and
rubella. Pneumococcal vaccine should be given once, as
soon as possible after HIV infection is diagnosed and then
a booster should be given at 5 years, and inuenza vaccine
should be given yearly. Live-virus vaccines should not be
given to persons with HIV infection.
PSYCHOSOCIAL ISSUES
HIV and AIDS affect all spheres of life.63 The psychological
effects of HIV infection or AIDS may be just as signicant
as the physical effects. The dramatic impact of this illness
is compounded by complex reactions on the part of the
person with HIV or AIDS; his or her partner, friends, and
family; members of the health care team; and the com-
munity. These reactions may be inuenced by inadequate
information, fear of contagion, shame, prejudices, and
condemnation of risk behaviors.64 Acknowledging a diag-
nosis of AIDS may be the rst indication to family and
colleagues of an otherwise hidden lifestyle (i.e., homo-
sexuality or drug use). This increases the strain on relation-
ships with important support persons. Shock is a common
reaction people have when they are diagnosed with HIV,
often followed by anger at themselves or others and denial
or guilt. In addition to the fear and grief associated with
death, the person with HIV or AIDS also may experience
uncertainty and may feel helpless, hopeless, stigmatized,
and out of control.63
Many people with HIV have preexisting mental
health conditions like depression or anxiety disorders as
well as alcohol and other drug problems (AODA). Appro-
priate diagnosis and treatment should be made available
when mental health or AODA problems are evident. Diag-
nosis and treatment of cognitive and affective disorders
are essential parts of ongoing care for the HIV-infected
442 UNIT V Inammation, Immunity, and Infection
person.63 The emotional stress, feelings of isolation, and
sadness experienced by the person with HIV or AIDS can
be overwhelming. Most persons, however, manage to
learn to cope and live with their HIV infection. Persons
with the disease must have as much information and con-
trol as possible. They should be encouraged to direct their
energies in a positive manner and continue with their so-
cial and group activities as long as such activities are help-
ful. Appropriate social support systems (e.g., AIDS service
organizations, community groups, religious organizations)
should be called on to assist whenever possible. When
they learn they can live with HIV infection, many persons
acquire a positive outlook based on living their lives to
the fullest.
In summary, because there is no cure for HIV, risk-free or low-
risk behavior is the best protection against HIV infection. Absti-
nence or long-term, mutually monogamous sexual relationships
between two uninfected partners, use of condoms, avoiding
drug use, and the use of sterile syringes are essential to stop-
ping the spread of HIV.
HIV is diagnosed using the EIA together with the Western
blot assay antibody detection tests. The emotional stress, feel-
ings of isolation, and sadness experienced by the person with
HIV or AIDS can be overwhelming, but most persons adjust to
living with HIV infection. Diagnosis and treatment of cogni-
tive and affective disorders are an essential part of ongoing
care for the HIV-infected person. Appropriate treatment should
be made available when alcohol or other drug dependence
is noted.
The management of HIV/AIDS incorporates the use of
HAART therapy, early recognition and treatment of oppor-
tunistic infections and other clinical disorders, as well as
acknowledgment and support of the psychosocial issues
that are an ongoing concern for those who are infected with
the virus.
HIV Infection in Pregnancy
and in Infants and Children
After completing this section of the chapter, you should be able to
meet the following objectives:
Discuss the vertical transmission of HIV from mother to
child and recommended prevention measures
Cite problems with the diagnosis of HIV infection in the
infant
Compare the progress of HIV infection in infants and
children with HIV infection in adults
Early in the AIDS epidemic, children who contracted
HIV could have become infected through blood products
or perinatally. Now, almost all of the children who be-
come infected with HIV at a young age in the United
States get HIV perinatally. Infected women may transmit
the virus to their offspring in utero, during labor and de-
livery, or through breast milk.65 The risk for transmission
is increased if the mother has advanced HIV disease as
evidenced by low CD4+ cell counts, high levels of HIV in
her blood (high viral load), or prolonged time from rup-
ture of membranes to delivery; if the mother breast-feeds
the child12; or if there is increased exposure of the fetus to
maternal blood.66
Diagnosis of HIV infection in children born to HIV-
infected mothers is complicated by the presence of maternal
HIV IgG antibody, which crosses the placenta to the fetus.12
Consequently, infants born to HIV-infected women can
be HIV antibody positive by ELISA for up to 18 months of
age even though they are not HIV infected. PCR testing for
HIV DNA is used most often to diagnose HIV in infants
younger than 18 months of age. Two positive PCR tests
for HIV DNA are needed to diagnose a child with HIV.
Children born to mothers with HIV infection are consid-
ered uninfected if they become HIV antibody negative after
6 months of age, have no other laboratory evidence of HIV
infection, and have not met the surveillance case denition
criteria for AIDS in children.
The landmark PACTG 076 trial of 1994 found that peri-
natal transmission could be lowered by two thirds, from
26% to 8%, by administering zidovudine to the mother dur-
ing pregnancy, labor, and delivery and to the infant when
it is born.11 The U.S. Public Health Service therefore recom-
mends that HIV counseling and testing should be offered to
all pregnant women.67 The recommendations also stress
that women who test positive for HIV antibodies should be
informed of the perinatal prevention benets of zidovudine
therapy and offered HAART therapy, which often includes
zidovudine. This is done because it has now been found
that women receiving antiretroviral therapy who also have
a viral load of less than 1000 copies/mL have very low rates
of perinatal transmission. Benets of voluntary testing for
mothers and newborns include reduced morbidity because
of intensive treatment and supportive health care, the op-
portunity for early antiviral therapy for mother and child,
and information regarding the risk for transmission from
breast milk.65
Because pregnant women in less developed countries
do not always have access to zidovudine, studies are being
conducted in Africa to determine whether any other sim-
ple and less expensive antiretroviral regimen can be used
to decrease transmission from mother to infant. One such
study, HIVNET 012, looked at single-dose nevirapine com-
HIV INFECTION IN PREGNANCY
AND IN INFANTS AND CHILDREN
HIV can be passed from mother to infant during labor and
delivery or through breast-feeding.
The course of HIV infection is different for children than
adults.

pared with zidovudine. It found that nevirapine lowered
the risk for HIV transmission by almost 50%.68
Children have a very different pattern of HIV infec-
tion than adults. Failure to thrive, CNS abnormalities, and
developmental delays are the most prominent primary
manifestations of HIV infection in children.12 Children
born infected with HIV usually weigh less and are shorter
than noninfected infants. A major cause of early mortality
for HIV-infected children is PCP. As opposed to adults, in
whom PCP occurs in the late stages, PCP occurs early in
children, with the peak age of onset at 3 to 6 months. For
this reason, prophylaxis with trimethoprim-sulfamethox-
azole is started by 4 to 6 weeks for all infants born to HIV-
infected mothers, regardless of their CD4+ cell count or
infection status.
In summary, infected women may transmit the virus to their
offspring in utero, during labor and delivery, or through breast
milk. It is recommended that all pregnant women get tested for
HIV. Diagnosis of HIV infection in children born to HIV-infected
mothers is complicated by the presence of maternal HIV anti-
body, which crosses the placenta to the fetus. This antibody
usually disappears within 18 months in uninfected children.
Administration of zidovudine to the mother during preg-
nancy, labor, and delivery and to the infant when it is born
can decrease perinatal transmission.
REVIEW EXERCISES
A 29-year-old woman presents to the clinic for her ini-
tial obstetric visit, about 10 weeks into her pregnancy.
A. This woman is in a monogamous relationship. Should
an HIV test be a part of her initial blood work? Why?
B. The womans HIV test comes back positive. What
should be done to decrease the risk for her passing on
HIV to her baby?
C. The baby is born, and its initial antibody test is posi-
tive. Does this mean the baby is infected? How is the
diagnosis of HIV in a baby younger than 18 months
made, and why is this different than the diagnosis for
adults?
A 40-year-old man presents to the clinic very short of
breath, and on x-ray and examination, he is diagnosed
with Pneumocystis carinii pneumonia (PCP). His provider
performs an HIV test, and the results are positive. Upon
further testing, the mans CD4+ count is found to be
100 cells/L, and his viral load is 250,000 copies/mL.
A. Why did the provider perform an HIV test after the
man was diagnosed with PCP?
B. Is there a way to prevent PCP?
C. What classication does this man fall into based on
his CD4+ count and symptomatology, and why?
CHAPTER 22 Acquired Immunodeciency Syndrome 443
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