GES 107

Introduction to Epidemiology of HIV and AIDS

Georgina N. Odaibo and Prof Olaleye

Department of Virology
COM, UI
 Definitions
• VIRUS
– A virus is the smallest known infective agent.
– They are also known as ‘filterable agent’
– Depend absolutely on the mechanisms of host cells for
survival.
– Outside the host, a virus is inert i.e they are non-living.
– Unlike other organism that possess both RNA and DNA,
the genetic material of viruses are either DNA or RNA.
– Not every virus will infect every cell; they have affinity
for specific host cell.
• For example HIV has affinity for CD4 bearing cells
• Hepatitis B virus has affinity for hepatocytes of the liver.
 AIDS
• Acquired Immunodeficiency Syndrome.
– Acquired
• means that the disease is not hereditary but from contact
with a disease-causing agent (in this case, HIV).
– Immunodeficiency
• means that the disease is characterized by a weakening of
the immune system.
– Syndrome
• refers to a group of symptoms that indicate or
characterize a disease.
 HIV
• Acronym for the Human Immunodeficiency virus,
the
• virus that causes acquired immunodeficiency
syndrome (AIDS).
• It is a retrovirus that has an RNA genome and a
reverse transcriptase enzyme.
– The usual direction of flow of genetic material is DNA
→RNA
– but retroviruses can go from RNA→DNA with the aid of
the reverse transcriptase (RT) enzyme
– The viral DNA integrates itself into the DNA of the host
and then take over the activity of the cell.
 Difference B/W HIV and AIDS
• AIDS is the late stage of HIV infection – the
presence of clinical disease
• HIV infected – the virus is present in the body
• Not everyone that is infected with HIV that
has AIDS
• Most HIV infected individuals will develop
AIDS if not on anti-retroviral drugs
Diagram of Human Immunodeficiency Virus-1

Function of HIV proteins

Gp 120: part of envelope- for attachment of virus
to cell
 Gp 41: part of envelope- used to internalize virus
into cell
 Lipid Membrane: envelope provides external
covering to the virus
 Integrase: enzyme used to integrate virus
genome to host genome
Reverse transcriptase: enzyme used to convert
viral RNA to viral cDNA that gets integrated into
the host genome
Viral RNA: Genome of the virus

Capsid: protein that surrounds the

genome/nucleic acid
 HIV TYPES AND SUBTYPES

• HIV is a highly variable virus which mutates very readily/easily

• This means there are many different strains of HIV, even within
the body of a single infected person.
• Based on genetic similarities and differences, HIV has been
classified into two types, HIV-1 and HIV-2.
• Both types are transmitted through the same mode and appear
to cause clinically indistinguishable AIDS.
• Worldwide, the predominant virus is HIV-1
• HIV-2 type is concentrated in West Africa and among those who
has lived or interacted with those from West Africa
SIMLARITIES AND DIFFERENCES BETWEEN
HIV-1 AND HIV-2

CHARACTERISTICS HIV-2 VERSUS HIV-1

Mode of transmission Same

Likelihood of perinatal transmission from 0.4% - 1.2% per birth for HIV-2 versus 25 – 35% per
mother to child birth per HIV-1

Likelihood of sexual transmission per sexual Approximately 3 fold reduced for HIV-2
exposure

Rate of development of AIDS <0.5% per year for HIV-2 versus 3 - 5% per year for
HIV-1 in some cohort

Rate of development of abnormal CD4+ Approximately 1% per year for HIV-2 versus 10% for
lymphocytes HIV-1

Distribution is Worldwide Distribution limited to West Africa

 HIV Subtypes
• HIV types are classified into groups which are further
classified into subtypes.

• HIV-1 can be classified into four groups: the "major" group

M, the "outlier" group O and two new groups, N and P.

• More than 90 percent of HIV-1 infections belong to HIV-1

group M.

• Within group M, at least nine genetically distinct subtypes

(or clades) of HIV-1 have been identified.
– These include subtypes A, B, C, D, F, G, H, J and K.
 Subtypes cont.
• HIV-1 also has unique property of recombination
– the ability of fragment of two or more subtypes to
come together and form a mosaic strain known as
‘circulating recombinant form (CRF).
– E.g. the CRF 02 which was first isolated in Ibadan by
Olaleye et al is a mixture of subtypes A and G
– The AG recombinant, alsoknown as IbNg (Ib-Ibadan
Ng-Nigeria) is the predominant subtype circulating
widely in West and Central Africa.
Genomic structure of a circulating recombinant form
(CRF02_AG)
 Global Distribution of HIV Subtypes
• Subtype B predominates in the Americas, Western Europe
and Australia
• Subtype C, a mixture of B, C, and BC recombinants
predominates in Asia
• Africa shows the greatest diversity of circulating HIV
subtypes and recombinants.
– Subtype C dominates the South and East (A and D also present)
– West and West Central Africa harbor mainly CRF02_AG, alongside
a complex array of other recombinants each present at a low
frequency
– The most complex epidemic is in Central Africa, where rare
subtypes and a wide variety of recombinant forms circulate
without any distinct predominant strain
 HIV-2 Subtypes
• There are 8 known HIV-2 subtypes (A to H).
• only groups A and B are epidemic.
• Group A spreads mainly in West Africa, but also
to Angola, Mozambique, Brazil, India and rarely
to Europe or the US.
• Group B is mainly confined to West Africa
 HIV CLASSIFICATION
HIV

Type 1 Type 2

A B C D E F G H
P
N (Non-M non-O)
M (Major) O (Outliers)

A B C D F G H J K >49 CRFs
• Infection with one particular HIV type or
subtype does not protect against infection with
other type/subtypes
– i.e multiple infection do occur
• New HIV genetic subtypes and CRFs
– may be discovered in the future
– current subtypes and CRFs will also continue to
spread to new areas as the global epidemic
continues.
 HOW HIV CAUSES AIDS

• HIV infects and destroys cells of the immune system known as

T-helper cells (CD4 bearing cells)

• The immune system is the arm of the body that defends and
protects the body against infection

• The T-helper cells are the most important cells of the immune
system; they play a central role, coordinating the activities of
other cells involved in the immune response

• There is a protein molecule on the surface of the T-helper cells

known as CD4 hence the T-helper cells are also known as CD4
bearing cells (CD4+).
Diagrammatical representation of the critical role of T4 Lymphocyte
in the Human Immune Response
 How HIV causes AIDS cont.
• Once the virus enters the cells
– it replicates in it and eventually destroys the cell,
– many virus particles are released which in turn infects other T-
helper cells and the cycle continues
• As the virus destroys the CD4 cells
– Initially, the body replaces them (long incubation period,
asymptomatic stage, clinical latency)
– their number reduces gradually to a point that the cells are not
enough to carry out their function of defending the body
effectively.
– The amount of virus circulating in the blood increases as the CD4
cells decreases

• At this point, opportunistic infections set in and this

individual is said to have developed AIDS
Virus and CD4 levels over the course of an
untreated HIV infection
 CD4 Count, Viral Load and Clinical
Course
Primary Sero-
Infection conversion

10,000,000 Intermediate Stage AIDS

CD4 Cell Count

1,000,000
Plasma HIV RNA

100,000

10,000 Viral Load

1,000 1,000
CD4 Cells
100
500
10

1
4-8 Weeks Up to 12 Years 2-3 Years
• People who are not infected with HIV and
generally are in good health have roughly 700
to 1,200 CD4+ T cells per microliter.
• This range varies by geographic location, race
and by age.
• In Nigeria, the CD4+ cell ranges from 365 to
1571 cell/ul in adults and 750 to 3000 cells/ul
in children bellow 12 years.
 Opportunistic infections
• infections that take advantage of the opportunity offered by a weakened immune
system to cause disease

• These are diseases that people with healthy immune systems can also get, but with HIV
they occur at a much higher rate.

• It also takes longer for a person with HIV to recover from these diseases than it takes for
someone with a healthy immune system.

• When the immune system is very weak due to advanced HIV disease or AIDS, some
opportunistic infections can spread to a number of different organs
– This is known as 'disseminated' or 'systemic' disease.
– Many of the opportunistic infections that occur at this late stage of HIV infection can
be fatal.

• Opportunistic infection may be caused by viruses, bacteria, fungi or parasites. A partial

list of the world's most common HIV-related opportunistic infections and diseases
includes:
 Opportunistic infections cont.
• Bacterial diseases such as
– tuberculosis, Mycobacterium Avium Complex (MAC), bacterial
pneumonia and septicaemia (blood poisoning)
• Protozoal diseases such as
– toxoplasmosis, microsporidiosis, cryptosporidiosis, isopsoriasis and
leishmaniasis
• Fungal diseases such as
– Pneumonistic Carini pneumonia (PCP), candidiasis, cryptococcosis and
penicilliosis
• Viral diseases such as
– those caused by cytomegalovirus, herpes simplex and herpes zoster
virus
• HIV-associated malignancies such as
– Kaposi's sarcoma, lymphoma and squamous cell carcinoma.
• Tuberculosis is the number one opportunistic infection in Africa.
 CLINICAL SYMPTOMS OF AIDS
 The following may be indication of advanced HIV infection:
– rapid weight loss
– dry cough
– recurring fever
– profuse night sweats
– profound and unexplained fatigue
– swollen lymph glands in the armpits, groin, or neck
– diarrhea that lasts for more than a week
– white spots or unusual blemishes on the tongue, in the mouth, or in the throat
– pneumonia
– red, brown, pink, or purplish blotches on or under the skin or inside the mouth, nose,
or eyelids
– memory loss, depression, and other neurological disorders

Each of these symptoms can be related to other illnesses.

Thus the only way to determine whether one is infected is to be tested for HIV infection
using laboratory techniques.
 DIAGNOSIS OF HIV INFECTION
• The effective control of HIV in any country must among other
measures depend on the establishment and provision of accurate and
reliable diagnostic techniques.

• The presence of HIV in the body courses the immune system to react
and produce a substance called antibodies.

• Routine diagnosis of HIV infection is based mainly on detection of

these HIV specific antibodies in the blood.

• Because the diagnosis of HIV infection in a particular person requires

a high degree of both sensitivity and specificity, the testing is done in
two stages
– screening and then confirmation.
Screening
High Sensitivity (Negative truly negative)
Antibody detection
 Specific HIV antibodies

• ELISA technique

• RAPID ASSAYS-agglutination, immunodot

(dipstick) etc.
• Blood/saliva/urine specimen could be used

• Best result obtained with blood samples

 CONFIRMATORY ASSAYS
High Specificity (Positive truly positive)
Antibody Detection
WB, IFA etc
Antigen Detection
 Detection of viral antigen-p24-ELISA
 Virus isolation-Cell culture

 Detection of viral nucleic acid-PCR

 EPIDEMIOLOGY OF HIV
In 2009, there were an estimated 2.6 million (1.8 million in sub-Saharan
Africa) people who became newly infected with HIV (UNAIDS, 2010)

Estimated 33.3 million people (22.5 million in sub-Saharan Africa) living with
HIV in 2009 (UNAIDS, 2010).

AIDS has caused death of an estimated 25 million people by 2007 (UNAIDS,

2008).

Estimated 1.8 million people (1.3 million in sub-Saharan Africa) including

about 260,000 children died of AIDS pandemic in 2009 alone (UNAIDS, 2010).
Responsible for one in five deaths in sub-Saharan Africa (UNAIDS and WHO,
2002).

About two-thirds (68%) of all people living with HIV reside in sub-Saharan
Africa (UNAIDS, 2010)
 The HIV Situation in Nigeria

• Nigeria has the third-largest number of people living with HIV in

the world
• The HIV epidemic in Nigeria is complex and varies widely by region
• The prevalence in the general population is determined by a
– National HIV sentinel survey among women attending antenatal clinics in
both the rural and the urban areas of the country
– The sentinel survey is repeated every two years in all states of the
Federation and FCT
• In some states, the epidemic is more concentrated, while other
states have more generalized epidemics

• The reason for the difference in the rate of infection is not very
clear, though some researchers have attributed it to difference in
sexual behaviour.
Fig:7 Geographical Distribution of HIV Prevalence by
States in Nigeria (FMOH, 2010)
 Nigeria situation cont.
• The first cases of HIV and AIDS in Nigeria were
reported in 1986
• The prevalence of the virus increased from
1.8% in 191 when the first sentinel survey was
conducted to a peak of 5.8% in the 2001
survey and then a drop to 5.0% in 2003
• 2010 survey showed that the National
prevalence has stabilized at about 4.0%
• Estimated 3.1 million adults are living with HIV
Trend of HIV prevalence in Nigeria
7

0
1991 1993 1995/6 1999 2001 2003 2005 2008 2010
 Nigeria situation cont.

• The main HIV transmission routes

– heterosexual sex which constitutes 90-95%,
– blood transfusions (2nd largest)
– and mother-to-child-transmission
• injection drug use and homosexual sex are
accounting for an increasing number of new
HIV infections hence their role in the spread of
the virus is becoming very important in
Nigeria.
– Study in Lagos report 45% among men having sex
with men (MSM)
 Nigeria situation cont.
• @ beginning- male to female ratio was
approximately 1:1
• recent data has shown that the rate is higher in
women (56%)
• Youth and young adults in Nigeria are
particularly vulnerable to HIV
– rate consistently high among 15-24 years
 Trend of HIV infection in the 15-49 age groups
in Nigeria
6

2003
3 2005
2008
2010

0
15-19 20-24 25-29 30-34 35-39 40-49
Differing
Differing subtype
subtype distribution
distribution within
within the
the
same
same state
state
 Nigeria situation cont.

• Major support on HIV/AIDS

– USG Presidents Emergency Plan for AIDS Relieve
(PEPFAR)
– Global fund
– World Bank
– FGN
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