GES 107Introduction to Epidemiology of HIV and AIDS

Georgina N. Odaibo and Prof OlaleyeDepartment 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 proteinsGp 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 genomeReverse transcriptase: enzyme used to convert viral RNA to viral cDNA that gets integrated into the host genomeViral 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 mother to child

0.4% - 1.2% per birth for HIV-2 versus 25 – 35% per birth per HIV-1

Likelihood of sexual transmission per sexual exposure

Approximately 3 fold reduced for HIV-2

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+ lymphocytes

Approximately 1% per year for HIV-2 versus 10% for 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 CLASSIFICATIONHIV

Type 2Type 1

N (Non-M non-O)

O (Outliers)

A B C D F G H J K >49 CRFs

M (Major)

A B C D E F G HP

• 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

1

10

100

1,000

10,000

100,000

1,000,000

10,000,000

Pla

sma

HIV

RN

A

Viral Load

CD4 Cells

4-8 Weeks Up to 12 Years 2-3 Years

CD

4 Cell C

ount

1,000

500

Intermediate Stage AIDS

Primary Infection

Sero-conversion

• 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 DetectionWB, IFA etc

Antigen Detection

Detection of viral antigen-p24-ELISA

Virus isolation-Cell culture

Detection of viral nucleic acid-PCR

EPIDEMIOLOGY OF HIVIn 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

1991 1993 1995/6 1999 2001 2003 2005 2008 20100

1

2

3

4

5

6

7

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

15-19 20-24 25-29 30-34 35-39 40-490

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6

2003200520082010

Differing subtype distribution within the same state

Differing subtype distribution within the same 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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