Lecture 9 - HIV/AIDS PDF

Lecture 9 — HIV/AIDS Dr. Ed El Sayed NURS 342 Objectives Origins of HIV Appearance of HIV in the US Virology and Epidemiology Prevention and Treatment Opportunistic Infections The origins of HIV i m The Simian Immunodeficiency Virus (SIV) infected monkeys centuries ago Hunter gatherers butchered mon...

Lecture 9 — HIV/AIDS Dr. Ed El Sayed NURS 342 Objectives Origins of HIV Appearance of HIV in the US Virology and Epidemiology Prevention and Treatment Opportunistic Infections The origins of HIV i m The Simian Immunodeficiency Virus (SIV) infected monkeys centuries ago Hunter gatherers butchered monkeys and consumed meat/organs Loading… Over time, SIV is thought to have mutated to become HIV 1 and HIV 2, capable of infecting humans (circa 1908) At first, not a lot of people were infected with HIV, and those infected were confined to certain geographic areas in Africa (circa 1920) With colonialism, slave trade, and reusing injections medically (sometimes experimentally), HIV disseminated globally Loading… In the United States of America… (1970s-1980s) Men who have sex with men traditionally socialized in public bath houses Mainly in New York City and San Francisco Then, in June 1981… Loading… class 6 What is a retrovirus? HIV is a ssRNA, enveloped retrovirus (reverse transcription) Subdivided into HIV 1 and HIV 2 (we will only focus on HIV 1) Belongs to Retroviridae family HIV is mainly a blood borne pathogen Non-sexual transmission is US is rare (screening blood banks, hygiene standards, etc.) but remains an issue in developing countries Primary route of sexual transmission worldwide: receptive vaginal sex among heterosexual persons Primary route of sexual transmission in US: receptive anal sex with ejaculation among men who have sex with men and transgender women Not all types of sex carry the same risk of HIV infection Vertical transmission rare in US, but remains an issue in subsaharan Africa and other “developing countries” Worldwide, there are 38 million persons living with HIV (1.1 million in US) Worldwide, there are 650K HIV related deaths per year (1.5 deaths per 100K persons in US) 51% of all HIV infected persons worldwide are women (majority are Black and Hispanic women) Highest infection incidence in US is among young men who have sex with men (primarily Blacks and Hispanics) Main HIV genes that encode for proteins: env — encodes envelope proteins pol — encodes enzymes required for replication (reverse transcriptase, protease and integrase) Loading… gag — encodes capsid and matrix proteins which are crucial for assembly of viral particle before cell exist, also used for diagnosis Many other HIV genes encode for important proteins (e.g. accessory genes), but our focus will only be on the three mentioned above CD4 is a type of surface receptors on immune cells, primarily T-cells HIV mainly targets CD4+ T-cells Attachment of the virus on the cell occurs via the viral GP120 First arm of the viral GP120 interacts with the CD4 receptor on the cell surface Second arm of the viral GP120 interacts with a co-receptor on the cell surface called CCR5 (other co-receptors exist but we will focus on CCR5 only) Once bona-fide communication occurs between GP120 and CD4/CCR5, the virus exposes another envelope protein called GP41 This exposed GP41 on the viral surface allows for the fusion of virus with cell membrane to complete the entry process Once inside the cell, reverse transcription begins in the cytoplasm Viral RNA is converted to DNA and this viral DNA is then transported to the nucleus Once in the nucleus, HIV DNA integrates with host DNA (with the help of the integrase enzyme) At this point, HIV DNA is referred to as “proviral DNA”, which will use the host polymerase enzymes and other cellular machinery to encode new copies of viral genes to be packaged and exported out of this cell to infect other cells Once integrated in the host genome, HIV remains in the cell for life Diagnosing HIV 1. Point of Care (POC): Rapid HIV test, available in community settings (e.g. pharmacy) Fingerpick test or saliva test Detect antibodies against HIV (approximately 45-90 days post infection) If positive, confirmation with lab test is needed for establishing the diagnosis 2. Fourth Generation Antigen/Antibody (Ag/Ab) Combo: Lab test — detects infection approximately 17-28 days post infection If positive, HIV RNA is quantified and CD4 count obtained to start treatment HIV “Window” Period Day 0 Potential exposure HIV RNA (NAAT) positive Days 7-14 4th Gen Ag/Ab positive Days 17-28 Days 45-90 POC Ab testing positive HIV RNA and CD4 count are inversely proportional Symptoms of HIV infection: Most cases will not experience any! In some patients, non-specific symptoms (aka “viral syndrome”) are present: malaise, fatigue, muscle aches, headache, fever, sore throat (these symptoms are usually short lived and confused with regular flu to cold virus) Virus becomes latent (i.e. establishes) reservoir, evades immune system and can reactivate at anytime Once CD4 count reaches a critical point (< 200), patents will start experiencing symptoms related to opportunistic infections or malignancy — this is called acquired immunodeficiency syndrome (AIDS) 50-yer-old man who has sex with men presents with low-grade fever, muscle aches, sore throat and palatal petechiae 7-days after having unprotected receptive anal sex HIV is not a vaccine preventable infection. Why? There is no proofreading mechanism in the reverse transcriptase: generates millions of “mutant” copies within the same replication cycle (1,000,000,000 copies/day!) There is no cure for HIV. Why? The integrated virus in host cells constitute what we refer to as “viral reservoir” — we do not know where all these reservoirs are or how big they are A sterilizing cure means the HIV genome must be “excised” from the host genome — we don’t know how to do that! However, HIV is a manageable infection (with our current medications, people living with HIV are able to live a long, healthy life) Antiretroviral therapy (ART) Many other ART agents exist! Therapy is one pill/day (this single pill contains at least 2 dugs) First-line regimens contain one integrase inhibitor + two NRTIs Long acting injectable: cabotegravir/rilpivirine combo Goals of therapy: 1. In individuals: undetected viral load and CD4 count > 200 2. In population: Decrease circulation of HIV in community What is PRE-exposure Prophylaxis (PrEP)? One pill taken orally once a day to prevent sexual transmission of HIV by more than 95%!!! Contains tenofovir+emtricitabine For persons at high risk for infection (regardless of gender or sexual orientation) PrEP is taken as long as their is risk for infection Contraindication: HIV infection!!! Cabotegravir anti-retro viral ARV belongs to INSTI I Nucleus Long-acting injectable given every 8-weeks Can be used solo to prevent infection (PrEP) be Can be used in combo with rilpivirine (NNRTI) to treat infection Must exclude active HIV infection before use as PrEP Need Additional “unique” contraindication — gluteal implants m m I can't I HIV test can't al active used to ensure PREPisok) inject ↓ cabotegrat What is POST-exposure Prophylaxis (PEP)? Used in situations with possible exposure to HIV in an individual not usually at risk for infection (e.g. needle prick of unknown source, rape victims) One pill taken orally daily for 28 days (contains one integrase plus two NRTIs) For maximum efficacy, HIV PEP must be initiated within 72 hours of possible exposure At the end of treatment period, drugs are discontinued and blood is drawn to check for HIV (if negative no need for ART, if positive, the pill is restarted for life) Opportunistic Infections (OIs) Pathogens that do not normally cause disease in immunocompetent patients CD4 count Associated OI risk In HIV infection, detectable viremia in the setting of low CD4 count is the biggest risk factor for OIs