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Genus RetroviridaeGenus Retroviridae

Lentivirus, which literally means slow virus Lentivirus, which literally means slow virus - it takes such a long time to develop - it takes such a long time to develop adverse effects in the body. adverse effects in the body.

This virus attacks the immune systemThis virus attacks the immune system

There are two strains – HIV 1 & HIV 2There are two strains – HIV 1 & HIV 2

These contain RNA, the genetic material These contain RNA, the genetic material of HIVof HIV

The outer layer of the HIV virus cell is The outer layer of the HIV virus cell is covered in coat proteins, which can bind covered in coat proteins, which can bind to certain WBCs. This allows the virus to to certain WBCs. This allows the virus to enter the cell, where it alters the DNA.enter the cell, where it alters the DNA.

The virus infects and destroys the CD4 The virus infects and destroys the CD4 lymphocytes which are critical to the lymphocytes which are critical to the body’s immune response.body’s immune response.

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The HIV virus first came to light during the The HIV virus first came to light during the early 1980’s. early 1980’s.

A number of healthy gay men in New York A number of healthy gay men in New York began to develop rare opportunistic infections began to develop rare opportunistic infections & cancers, that were resistant to treatment.& cancers, that were resistant to treatment.

One such viral opportunistic infection is One such viral opportunistic infection is cytomegalovirus that causes blindness & cytomegalovirus that causes blindness & inflammation of the coloninflammation of the colon

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The emergence of HIV & AIDS has resulted The emergence of HIV & AIDS has resulted in countless debates as to where it in countless debates as to where it originated fromoriginated from

It’s suspected that it originated from S.I.V It’s suspected that it originated from S.I.V (Simian Immunodeficiency Virus)(Simian Immunodeficiency Virus)

SIV affects MonkeysSIV affects Monkeys

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RNA virus, 120nm in diameter

Envelope gp160; gp120 & gp41

Icosahedral symmetry Nucleocapsid

Outer matrix protein (p17) Major capsid protein (p24) Nuclear protein (p7)

Diploid RNA with several copies of reverse transcriptase

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Subtype C is predominant in Southern and East Africa, India and Nepal.

It has caused the world's worst HIV epidemics and is responsible for around half of all infections.

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The virus are inactivated in 10 minutes at 600c and in seconds at 1000c

At room temperature survive for seven days HIV are inactivated in 10 minutes by

treatment with 50% ethanol 35% Isopropanol. 0.5% Lysol and paraformaldehyde 0.3% hydrogen 10% house hold bleach Hypochlorite solution at 0.5% 2% Glutaraldehyde

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Within the inflammatory cells of the infection (T cells)

Site of replication shifts to lymphoid tissues:Lymph nodesSpleenLiverBone marrow

Macrophages and Langerhans cells become reservoirs and sites of replication but do not die themselves.

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3 areas:3 areas:

1. Destruction of CD4+ T cells 1. Destruction of CD4+ T cells populationpopulation

2. Immune effects due to HIV 2. Immune effects due to HIV infectioninfection

3. Progression of HIV infection to 3. Progression of HIV infection to AIDSAIDS

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2.Host’s immune responses2.Host’s immune responses

Both humoral and cell-mediated immune Both humoral and cell-mediated immune responses partially control the viral production responses partially control the viral production but in this process they destroy the infected but in this process they destroy the infected CD4+T cells, leading to a gradual decline of CD4+T cells, leading to a gradual decline of CD4+ T cellsCD4+ T cells

HIV-specific CTLs kill infected CD4+ T cellsHIV-specific CTLs kill infected CD4+ T cells

Antibodies that recognize a variety of HIV Antibodies that recognize a variety of HIV antigens are produced - Antibody dependent cell-antigens are produced - Antibody dependent cell-mediated cytotoxicitymediated cytotoxicity

Apoptosis of infected cellsApoptosis of infected cells

Blood Semen/Vaginal fluids (as high as blood)

Breast milk Pus from sores

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It is highly unlikely you will be infected if you come into contact with:

Sweat Tears Urine Saliva (-highly possible if blood from

mouth sores is present)

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1. Males, homosexuals & bisexuals2. IV drug users3. Improperly screened transfusion recipients4. Sexual partners of persons infected with HIV5. Infants of HIV –infected mothers

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ANY type of sexual activity (highest risk) Sharing used drug needles Pregnancy-from mother to child Sharing razors- if blood is present Kissing- if even the smallest amount of blood

is present. (-membranes of mouth are thin enough for HIV to enter straight into the body.)

Tattoos/body piercing if equipment is not clean.

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Semen11,000 Vaginal

Fluid7,000

Blood18,000

Amniotic Fluid4,000 Saliva

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Average number of HIV particles in 1 ml of these body fluids

Vaginal Intercourse Anal Intercourse (10x higher infection

rate than vaginal intercourse because of tissue tear is higher

Oral Intercourse Blood Transfusion (risk greater than

90% if sample is already infected) Needles (tattoos, injections) Infected mother to the infant through: Pregnancy (placenta), Birth, and

breastfeeding

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This is the period of time after becoming infected when an HIV test is negative

90 percent of cases test positive within three months of exposure

10 percent of cases test positive within three to six months of exposure

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HIVVirus

T-CellHIV Infected

T-Cell

New HIVVirus

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B cells – impaired humoral responseB cells – impaired humoral response

B-cell hyper reactivity B-cell hyper reactivity Polyclonal hypergammaglobulinemia due to enhanced Polyclonal hypergammaglobulinemia due to enhanced

nonspecific IgG and IgA production.nonspecific IgG and IgA production. Impaired Ab-isotype switching and inability to respond to Impaired Ab-isotype switching and inability to respond to

specific antigen.specific antigen. High incidence of B-cell lymphomas High incidence of B-cell lymphomas

Lymph nodesLymph nodes

HIV kills cells in the lymph nodesHIV kills cells in the lymph nodes Early HIV infection: destruction of dendritic cellsEarly HIV infection: destruction of dendritic cells Late stage: extensive damage, tissue necrosis, a loss of Late stage: extensive damage, tissue necrosis, a loss of

follicular dendritic cells and germinal centres.follicular dendritic cells and germinal centres. An inability to trap Ag or support activation of T+B cellsAn inability to trap Ag or support activation of T+B cells

normal

Severely impaired

Abnormal

Slightly reduced

Time

Acute HIV disease

Exposure to HIV

Clinical latency period-declining CD4+ T cell amount

AIDS

Imm

une

com

pete

nce

Opportunistic infections

Progression of HIV infection

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After initial infection with After initial infection with HIV, there is usually an HIV, there is usually an acute flu-like illness.acute flu-like illness.

This illness may includeThis illness may include Fever Fever Headache Headache Tiredness Tiredness Enlarged lymph nodesEnlarged lymph nodes

But after this most But after this most individuals are clinically individuals are clinically asymptomatic for years. asymptomatic for years. This is called the clinical This is called the clinical latency period.latency period.

Short, flu-like illness - occurs one to six weeks after infection

no symptoms at all Infected person can infect other people

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Lasts for an average of ten years This stage is free from symptoms There may be swollen glands The level of HIV in the blood drops to very low

levels HIV antibodies are detectable in the blood

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The symptoms are mild The immune system deteriorates Emergence of opportunistic infections and

cancers

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The immune system weakens

The illnesses become more severe leading to an AIDS diagnosis

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During the latency period, lymph nodes and the spleen are During the latency period, lymph nodes and the spleen are sites of continuous HIV replication and cell destruction. sites of continuous HIV replication and cell destruction.

The immune system remains competent at handling most The immune system remains competent at handling most infections with opportunistic microbes but the number of infections with opportunistic microbes but the number of CD4+ T cells steadily declines.CD4+ T cells steadily declines.

Symptoms often experienced months to years before the Symptoms often experienced months to years before the onset of AIDS.onset of AIDS.

Lack of energy Lack of energy Weight loss Weight loss Frequent fevers and sweats Frequent fevers and sweats Persistent or frequent yeast infections Persistent or frequent yeast infections Persistent skin rashes Persistent skin rashes Dysfunction of CNSDysfunction of CNS

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Final Final stage of HIV infection - AIDS stage of HIV infection - AIDS

Occurs when the destruction of peripheral lymphoid tissue is Occurs when the destruction of peripheral lymphoid tissue is complete and the blood CD4+ T cell count drops below complete and the blood CD4+ T cell count drops below 200 200 cells/mmcells/mm33. (Healthy adults usually have CD4+ T-cell counts . (Healthy adults usually have CD4+ T-cell counts of 1,000 or more). of 1,000 or more).

AIDS – acquired immunodeficiency syndrome – is marked by AIDS – acquired immunodeficiency syndrome – is marked by development of various opportunistic infections and development of various opportunistic infections and malignancies.malignancies.

The level of virus in the blood and CD4+ T cell count can The level of virus in the blood and CD4+ T cell count can predict the risk of developing AIDS. Vpredict the risk of developing AIDS. Voral titers often oral titers often accelerate as the patient progresses towards AIDS.accelerate as the patient progresses towards AIDS.

Without treatment, at least 50% of people infected with HIV Without treatment, at least 50% of people infected with HIV will develop AIDS within ten years.will develop AIDS within ten years.

Before Birth During Birth Postpartum

After the birth

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Shaking hands Hugging Swimming pools

Toilet seats Insect bites Donating blood

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No individual should be made to undergo a mandatory testing for HIV

No mandatory HIV testing should be imposed as a precondition for - Employment - Providing health care services and facilities

Any HIV testing must be accompanied by a pretest and posttest counseling services (through VCTC)

Testing without consent – hindrance to the control of the epidemic

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Transmission Prevention Risk Factors Voluntary & Confidential

Report ability of Positive Test Results

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Clarifies test results

Need for additional testing

Promotion of safe behavior

Release of results

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(i) Screening tests - ELISA and simple/rapid tests.

(ii) Confirmatory or supplemental tests-

Western Blot assay. (iii) Nucleic acid and antigen

screening tests. Polymerase chain reaction (PCR), Ligase chain reaction (LCR), Nucleic acid based Sequence assays (NASBA) and some ELISA tests.

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Initial test for HIV is an indirect ELISA test Initial test for HIV is an indirect ELISA test Economic, rapid, performed easily, high sensitivity Economic, rapid, performed easily, high sensitivity

and specificityand specificity Detects anti-HIV antibodies in patient serumDetects anti-HIV antibodies in patient serum Antibodies are generally detectable within 3 Antibodies are generally detectable within 3

months of infectionmonths of infection Antibodies are typically directed at the envelope Antibodies are typically directed at the envelope

glycoproteins (gp120 and gp41)glycoproteins (gp120 and gp41)

Absence of antibody, as in ‘window Absence of antibody, as in ‘window period’ does not exclude the period’ does not exclude the presence of the virus which can be presence of the virus which can be detected by PCR amplification detected by PCR amplification approx. ten days after infectionapprox. ten days after infection

‘‘Window period’ – time between Window period’ – time between infection and detection of serological infection and detection of serological viral markerviral marker

Direct ELISA for p24 antigen canDirect ELISA for p24 antigen can also also be used although the false negative be used although the false negative rate is higherrate is higher

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EIA/ELISATest

PositiveNegative

Run IFAConfirmation

RepeatPositive

Positive

End Testing

Repeat ELISAEvery 3 months

for 1 year

Negative

PositiveNegativeIndeterminate

Repeat at 2-4 months

Repeat at 3 weeks

HIV Testing

No HIV ExposureLow Risk

HIV ExposureHigh Risk

NegativeHIV

+

Repeat every 6 months for continued

High risk behavior

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Confirms HIV infectionConfirms HIV infection Proteins are separated by electrophoresis and Proteins are separated by electrophoresis and

transferred to a nitrocellulose membrane by the transferred to a nitrocellulose membrane by the passage of an electric currentpassage of an electric current

The proteins are treated with antibodiesThe proteins are treated with antibodies Similar to ELISA technique, addition of secondary Similar to ELISA technique, addition of secondary

antibodies with an enzyme attached allows the use antibodies with an enzyme attached allows the use of colour to detect a particular proteinof colour to detect a particular protein

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ADVANTAGES:ADVANTAGES: quicker to perform

do not require batchingdo not require specialised equipment or

trained personnel results delivered on the same day

Only ‘WHO recommended’ Rapid HIV antibody tests should be used to ensure quality.

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Follows acute infection with HIV, before HIV antibodies can be detected in the patient’s blood stream.

Patient is highly infectious, despite testing HIV antibody negative, HIV is replicating rapidly in all body compartments.

Typically up to 12 weeks duration but may be shorter in more sensitive HIV antibody assays.

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Infants born to HIV infected mothers will have antibodies to HIV in their serum as a result of:maternal-fetal transfer during pregnancydelivery breast-feeding

they may not necessarily be infected !

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Eradication of HIV infection not possible with currently Eradication of HIV infection not possible with currently available drugsavailable drugs

Viral replication can not be completely suppressedViral replication can not be completely suppressed Latently infected CD4+ T cells established at early Latently infected CD4+ T cells established at early

stagestage Goals of antiretroviral therapy are to:Goals of antiretroviral therapy are to:

- Suppress viral replication- Suppress viral replication- Restore and/or preserve immune function- Restore and/or preserve immune function- Improve quality of life - Improve quality of life - Reduce HIV-associated morbidity and mortality- Reduce HIV-associated morbidity and mortality

Combinations of antiretroviral drugs are usedCombinations of antiretroviral drugs are used Referred to as HAART (highly active antiretroviral Referred to as HAART (highly active antiretroviral

therapy)therapy) Suppress levels of plasma viraemia for long periodsSuppress levels of plasma viraemia for long periods Plasma viraemia is a strong prognostic factor in HIV Plasma viraemia is a strong prognostic factor in HIV

infectioninfection

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Significant declines in AIDS related morbidity and Significant declines in AIDS related morbidity and mortality are seen as a result of HAARTmortality are seen as a result of HAART

Several strategies for development of effective antiviral Several strategies for development of effective antiviral drugsdrugs

Potential therapies based on knowledge of the way in Potential therapies based on knowledge of the way in which HIV gains access into the cells and its method of which HIV gains access into the cells and its method of replication replication

Targets for therapeutic anti-retroviral drugs:Targets for therapeutic anti-retroviral drugs:

- Inhibiting reverse transcription- Inhibiting reverse transcription

- Inhibiting proteases- Inhibiting proteases

- Inhibiting integrate – interferes with integration of viral - Inhibiting integrate – interferes with integration of viral DNA into host genome DNA into host genome

- Inhibiting fusion – prevents virus from fusing with host cell- Inhibiting fusion – prevents virus from fusing with host cell

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Combination of RT inhibitors protease inhibitors Combination of RT inhibitors protease inhibitors results in potent anti-viral activityresults in potent anti-viral activity

In most cases, two nucleoside analogues and one In most cases, two nucleoside analogues and one protease inhibitor are taken togetherprotease inhibitor are taken together

HAART lowers plasma viral loads in many cases to HAART lowers plasma viral loads in many cases to levels not detectable by current methods levels not detectable by current methods

Has improved the health of AIDS patients to the Has improved the health of AIDS patients to the point that they can function at a normal levelpoint that they can function at a normal level

Nucleoside Reverse Transcriptase inhibitorsAZT (Zidovudine)

Non-Nucleoside Transcriptase inhibitorsViramune (Nevirapine)

Protease inhibitorsNorvir (Ritonavir)

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Education Prevention of blood born HIV

transmission Anti Retro Viral treatment Combination therapy Post exposure prophylaxis Specific prophylaxis Primary health care

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World AIDS Day, observed December 1 each year, is dedicated to raising awareness of the AIDS pandemic caused by the spread of HIV infection. It is common to hold memorials to honour persons who have died from HIV/AIDS on this day. Government and health officials also observe the event, often with speeches or forums on the AIDS topics.

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