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Dr.T.V.Rao MD
Beginning of HIV/AIDS
The first published article related to AIDS was in 1981. The principal authors name was Michael Gottlieb and it appeared in the Morbidity and Mortality Weekly Report for June 5th. This article reported that there was a random increase in pneumocystis carinii pneumonia (PCP), a rare lung infection.
Dr.T.V.Rao MD
Learn about:
HIV The immune system CD4 cells Checking how the immune system is working Viral load Why some people with HIV are well and others are very sick How you get HIV
History of HIV
The HIV virus first came to light during the early 1980s. A number of healthy gay men in New York began to develop rare opportunistic infections & cancers, that were resistant to treatment. One such viral opportunistic infection is cytomegalovirus that causes blindness & inflammation of the colon
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What is Human Immune Deficiency Virus Genus Reoviridae Lentivirus, which literally means slow virus - it takes such a long time to develop adverse effects in the body. This virus attacks the immune system
There are two strains HIV 1 & HIV 2
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HIV is a Virus.
H: Human I:Immunodeficiency V: Virus
HIV Origins
Research teams in the U.S.A & France made independent research discoveries of the virus. French researchers discovered a virus linked to AIDS in 1983, they called it Lymphadenopathy-Associated Virus (LAV) In 1984, American researchers isolated a virus that caused AIDS, calling it Human T-lymph tropic Virus type III (HTLV- III ) These two viruses were later found to be the same virus - HIV
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Retroviral Genes
gag (group-specific antigen): makes the cone shape viral capsid. pol (polymerase): codes for viral enzymes reverse transcriptase, integrase, and viral protease. env (envelope): makes surface protein gp120 and trans membrane gp41, enabling HIV to fuse to CD4 cells.
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Other genes
Tat The Tran activator gene influences the function of genes some distance away. It controls transactivation of all HIV proteins. rev The differential regulator of expression of virus protein genes. vif The virus infectivity factor gene is required for infectivity as cell-free virus. nef The negative regulator factor retards HIV replication. vpr The virus protein R gene has an undetermined function..
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Types of HIV
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Resistance
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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HIV Replication
Attachment Penetration Uncoating Reverse Transcription Integration Replication Assembly Release
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2. Fusion: Viral envelope fuses with cell membrane, releasing contents into the cell.
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The gp41 portion is half embedded in the membrane envelope and interacts with gp120 portion on the exterior side of the membrane.
Each receptor is composed of 3 subunits of gp41 and 3 subunits of gp120.
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CD4 cells
CD4 cell are destroyed after HIV uses them to make more HIV. The bodys immune system works hard making more CD4 cells.
2002 Boehringer Ingelheim GmbH
Lifecycle of HIV
HIV particles enter the body in a fluid as it can not survive without a support medium. The virus targets any cell expressing CD4, including T helper cells, macrophages, dendritic cells and Dr.T.V.Rao MD monocytes.
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Transcription: Viral RNA is converted into DNA by unique enzyme reverse transcriptase.
Reverse transcriptase
RNA ---------------------> DNA Reverse transcriptase is the target of several HIV drugs: AZT, ddI, and ddC.
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Blood Semen/Vaginal fluids (as high as blood) Breast milk Pus from sores
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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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Blood 18,000
Semen 11,000
Saliva 1
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Transmission
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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Window Period
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 Dr.T.V.Rao MD
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1. Destruction of CD4+ T cells population 2. Immune effects due to HIV infection 3. Progression of HIV infection to AIDS
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T-Cell
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Immune responses fail to eradicate all viruses. Viral load is maintained at low level Continuous decline of CD4+ T cells
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Category 3: < 200 cells/mm3 (or CD4% < 14%)(CD4+ T-lymphocyte counts per microliter of blood)
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But after this most individuals are clinically asymptomatic for years. This is called the clinical latency period.
Immune competence
This illness may include Fever Headache Tiredness Enlarged lymph nodes
Slightly reduced
Abnormal
AIDS
Severely impaired
Opportunistic infections
Time
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Stage 1 - Primary
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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Stage 2 - Asymptomatic
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
Stage 3 - Symptomatic
The symptoms are mild The immune system deteriorates Emergence of opportunistic infections and cancers
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Progression to AIDS
During the latency period, lymph nodes and the spleen are sites of continuous HIV replication and cell destruction.
The immune system remains competent at handling most infections with opportunistic microbes but the number of CD4+ T cells steadily declines.
Symptoms often experienced months to years before the onset of AIDS. Lack of energy Weight loss Frequent fevers and sweats Persistent or frequent yeast infections Persistent skin rashes Dysfunction of CNS
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Progression to AIDS
Final stage of HIV infection - AIDS
Occurs when the destruction of peripheral lymphoid tissue is complete and the blood CD4+ T cell count drops below 200 cells/mm3. (Healthy adults usually have CD4+ T-cell counts of 1,000 or more). AIDS acquired immunodeficiency syndrome is marked by development of various opportunistic infections and malignancies.
The level of virus in the blood and CD4+ T cell count can predict the risk of developing AIDS. Voral titers often accelerate as the patient progresses towards AIDS. Without treatment, at least 50% of people infected with HIV will develop AIDS within ten years. Dr.T.V.Rao MD 61
Opportunistic Infections
Mother-to-Baby
Before Birth During Birth Postpartum
After the birth
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Counseling
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Transmission Prevention Risk Factors Voluntary & Confidential Report ability of Positive Test Results
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Post-test Counseling
Clarifies test results Need for additional testing Promotion of safe behavior Release of results
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Diagnosis of
HIV and AIDS
(ii) Confirmatory or supplemental testsWestern 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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Diagnosis of HIV
Initial test for HIV is an indirect ELISA test Economic, rapid, performed easily, high sensitivity and specificity Detects anti-HIV antibodies in patient serum Antibodies are generally detectable within 3 months of infection Antibodies are typically directed at the envelope glycoproteins (gp120 and gp41)
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HIV Testing
EIA/ELISA Test
Negative No HIV Exposure Low Risk Negative HIV Exposure High Risk Repeat ELISA Every 3 months for 1 year Repeat every 6 months for continued High risk behavior End Testing Negative
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Positive
Positive
Positive
HIV
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Diagnosis of HIV
Positive or indeterminate ELISA tests for antiHIV antibodies are confirmed by immunoblotting (Western Blotting) which identifies specific HIV virus proteins PCR can also be used Detects pro-viral DNA or viral RNA It is highly sensitive and specific but is more costly than ELISA Can be used to test infants born to HIV-infected mothers
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Confirms HIV infection Proteins are separated by electrophoresis and transferred to a nitrocellulose membrane by the passage of an electric current The proteins are treated with antibodies Similar to ELISA technique, addition of secondary antibodies with an enzyme attached allows the use of colour to detect a particular protein
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Western Blotting
A discrete protein band represents the specific antigen that the antibody recognizes The bands from a positive Western blot are from antibodies binding to specific proteins and glycoprotein's from the HIV virus The CDC recommends that the blot should be positive for two of the p24, gp41 and gp120/160 markers (gp160 is the precursor form of gp41 and gp120, the envelope protein)
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Understanding viral load LOW viral load is less than 10,000 copies.
HIGH viral load is more than 10,000 copies.
Rapid Tests
ADVANTAGES:
quicker to perform
do not require batching do 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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Treatment of HIV
Eradication of HIV infection not possible with currently available drugs Viral replication can not be completely suppressed Latently infected CD4+ T cells established at early stage Goals of antiretroviral therapy are to: - Suppress viral replication - Restore and/or preserve immune function - Improve quality of life - Reduce HIV-associated morbidity and mortality Combinations of antiretroviral drugs are used Referred to as HAART (highly active antiretroviral therapy) Suppress levels of plasma viraemia for long periods Plasma viraemia is a strong prognostic factor in HIV Dr.T.V.Rao MD 87 infection
HIV uses parts of the CD4 cell to make more virus (replicate). During this process the CD4 cell is destroyed.
AIDS
A Acquirednot inherited I Immunoattacks the immune system D Deficiency destroys CD4 cells S Syndromea group of symptoms or illnesses
Section 2
Understanding Antiretroviral Therapy
Learn about:
Highly active antiretroviral therapy (HAART) How HAART works Adherence Resistance Side effects Why HAART sometimes doesnt work well
Treatment of HIV
Eradication of HIV infection not possible with currently available drugs Viral replication can not be completely suppressed Latently infected CD4+ T cells established at early stage Goals of antiretroviral therapy are to: - Suppress viral replication - Restore and/or preserve immune function - Improve quality of life - Reduce HIV-associated morbidity and mortality Combinations of antiretroviral drugs are used Referred to as HAART (highly active antiretroviral therapy) Suppress levels of plasma viraemia for long periods Plasma viraemia is a strong prognostic factor in HIV Dr.T.V.Rao MD 99 infection
Antiretroviral Drugs
Significant declines in AIDS related morbidity and mortality are seen as a result of HAART Several strategies for development of effective antiviral drugs Potential therapies based on knowledge of the way in which HIV gains access into the cells and its method of replication Targets for therapeutic anti-retroviral drugs: - Inhibiting reverse transcription - Inhibiting proteases - Inhibiting integrate interferes with integration of viral DNA into host genome - Inhibiting fusion prevents virus from fusing with host cell
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Antiretroviral Drugs
Nucleoside Reverse Transcriptase inhibitors
AZT (Zidovudine)
Protease inhibitors
Norvir (Ritonavir)
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HAART
Missed doses
If doses are missed, medicines may cease to be effective.
Adherence
Doctors, nurses, counsellors, family and friends provide support for taking medicines.
Monitoring treatment
Side effects
Most side effects are mild and temporary, but others are more serious. If side effects occurtalk to your clinician.
Treatment failure
Missed doses Viral resistance Medicines not taken due to side effects Other medicines interfere Advanced HIV disease
Play safe
Use the common sense Be faithful to one partner, Use Condom. Antiretroviral drugs Caesarean delivery
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Abstinence
It is the only 100 % effective method of not acquiring HIV/AIDS. Refraining from sexual contact: oral, anal, or vaginal. Refraining from intravenous drug Dr.T.V.Rao MD
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Monogamous relationship
A mutually monogamous (only one sex partner) relationship with a person who is not infected with HIV HIV testing before intercourse is necessary to prove your partner is not infected
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AIDS
Move from Past to Future
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