Retroviruses & HIV/AIDS PDF

# Retroviruses & HIV/AIDS ## Outline - Distribution - Classification - Characteristics - Pathogenesis - Clinical manifestations - Antiretroviral drugs - Prevention strategies ## Global HIV Statistics - 38.4 million [33.9 million-43.8 million] people globally were living with HIV in 2021. - 1.5 mil...

# Retroviruses & HIV/AIDS ## Outline - Distribution - Classification - Characteristics - Pathogenesis - Clinical manifestations - Antiretroviral drugs - Prevention strategies ## Global HIV Statistics - 38.4 million [33.9 million-43.8 million] people globally were living with HIV in 2021. - 1.5 million [1.1 million-2.0 million] people became newly infected with HIV in 2021. - 650 000 [510 000-860 000] people died from AIDS-related illnesses in 2021. - 28.7 million people were accessing antiretroviral therapy in 2021. - 84.2 million [64.0 million-113.0 million] people have become infected with HIV since the start of the epidemic. - 40.1 million [33.6 million-48.6 million] people have died from AIDS-related illnesses since the start of the epidemic. ## Global distribution: 2021 This is a world map showing the estimated number of adults and children living with HIV in 2021. | Region | Estimated number of people living with HIV | |---|---| | North America and western and central Europe | 2.3 million [1.9 million-2.6 million] | | Caribbean | 330 000 [290 000-380 000] | | Latin America | 2.2 million [1.5 million-2.8 million] | | Middle East and North Africa | 180 000 [150 000-210 000] | | Western and central Africa | 5.0 million [4.5 million-5.6 million] | | Eastern and southern Africa | 20.6 million [18.9 million-23.0 million] | | Eastern Europe and central Asia | 1.8 million [1.7 million-2.0 million] | | Asia and the Pacific | 6.0 million [4.9 million-7.2 million] | **Total: 38.4 million [33.9 million-43.8 million]** ## Kenya This is a map of Kenya showing the prevalence of HIV in each county. - Prevalence= 6% - PLHIV: 1.6M - 192,000 infected children - New infections: 102,000 p.a. - Deaths: 58,000 p.a. ## Key Populations This image shows three red circles representing key populations at risk for HIV infection. - **Sex workers: 29%** - **PWIDs: 18%** - **MSM: 18%** Key populations: 2% of the population; a third of all new infections (MOTs) ## Origin Of HIV This is a phylogenetic tree showing the evolutionary relationships between different strains of HIV and their simian immunodeficiency virus (SIV) ancestors. - HIV-1 Group M originated from chimpanzees ( _Pan troglodytes troglodytes_ ) in the early 1900s. - HIV-2 originated from sooty mangabeys ( _Cercocebus atys_ ) in the early 1920s. ## Retroviridae Family This is a table showing the classification of the Retroviridae family. | Subfamily | Genera | Species (Examples) | |---|---|---| | Orthoretrovirinae | Alpharetrovirus | e.g. Rous sarcoma virus | | | Betaretrovirus | e.g. Mouse mammary tumor virus | | | Deltaretrovirus | e.g. Human T-Lymphotropic virus(HTLV) | | | Epsilonretrovirus | Walleye dermal sarcoma virus | | | Gammaretrovirus | Viper retrovirus, Porcine type C oncovirus | | | **Lentivirus** | HIV-1, HIV-2, SIV, BIV, FIV, EIAV | | Spumaretrovirinae | Spumavirus | Equine foamy virus | ## Retroviruses Unique features: - Undergo reverse transcription - Three common genes, ( _gag_, _pol_, _env_ ) in all retroviruses - 2 copies of ss (+)sense RNA ## HIV - Baltimore: Group 6 (ssRNA + Reverse Transcriptase) - ICTV(International Committee on Taxonomy of Viruses): - Family: Retroviridae - Genus: Lentiviruses - Species: HIV-1 & HIV-2 - Groups: HIV 1 – M, N, O&P - Clades: HIV-1 (A-K, CRFs); HIV-2 (A-H) ## HIV Subtypes (Clades) This is a diagram showing the classification of HIV subtypes or clades. - HIV-1: - Group M: A, B ,C, D, F, G ,H ,J, K, CRFS - Group N - Group O - Group P - HIV-2: A-H ## HIV-1 vs HIV-2 | Feature | HIV-1 | HIV-2 | |---|---|---| | Distribution | Worldwide | West Africa, Europe & USA | | Transmission | Easier transmission | Less easily transmitted | | Progression | Faster progression | Slower progression | | Origin | Related to SIV_cpz_ (Chimpanzee SIV) | Related to SIV_sm_ (Sooty Mangabey SIV) | | Treatment | Responds to NNRTIS\* | No response to NNRTIS: e.g. EFV, NVP | *NNRTIS = Non-nucleoside Reverse Transcriptase Inhibitors ## HIV Particle Structure This is a diagram of the HIV particle, showing its various components. - Nucleocapsid - Protease - Vif, Vpr - Nef & p7 - Reverse Transcriptase - Integrase - RNA - gp120 - gp41 - gag p17 - Lipid Membrane - gag p24 ## HIV Ligand-Cell Receptor Interaction - Ligand: HIV glycoprotein gp120 - Cellular Receptor: CD4 - Co-receptors: CCR-5 or CXCR4 - HIV requires CD4 Receptor & a co-receptor for entry - The receptors/co-receptors are expressed by immune cells (T-Cells and Antigens Presenting Cells) ## Retrovirus Replication Cycle This is a diagram of the HIV replication cycle, showing the seven steps involved. 1. Entry 2. Reverse Transcription 3. Integration 4. Transcription 5. Translation 6. Maturation 7. Budding ## Transmission of HIV - Sexual contact: oral, anal, vaginal - Sharps – needles, blades - Blood transfusion - MTCT: during pregnancy, delivery, or breastfeeding ## Risk Factors: Acquisition Of HIV Infection - Nature of the exposure (the dose of HIV inoculum) - Host susceptibility to infection (host genetics e.g. delta 32 mutation) - Routes of transmission (intravenous> Rectal > Vaginal) - Mucosal inflammation (ulceration by STDs) ## Sequence Of Events In HIV Infection - HIV infects CD4 cells (APC) - Disseminated infection - Specific immune Response (Ab, CMI) - Clearance of most virus - Some persistence - a) Gradual loss of CD4 cells - b) Destruction of lymphoid tissue ## Clinical Features 1. Primary stage/Acute retroviral syndrome - Seen in 10% of individuals a few weeks after exposure - Acute seroconversion - Presents with an ‘flu-like' illness & lymphadenopathy 2. Asymptomatic stage - Months to >10 years - Incubation period is 8-10 years 3. Symptomatic and AIDS Stage - Opportunistic infections - AIDS defining illnesses & cancers set in ## Opportunistic Infections This is a table showing opportunistic infections caused by HIV. | Type | Examples | |---|---| | Protozoal | Toxoplasmosis, crytosporidiosis, Isosporiasis, | | Fungal | Candidiasis, Crytococcosis, Histoplasmosis, Coccidiodomycosis, PCP pneumonia | | Bacterial | TB, Salmonella septicaemia, Multiple or recurrent pyogenic bacterial infection (meningitis, pneumonia, pyomyositis etc.) | | Viral | CMV, HSV, VZV | ## Opportunistic Infections/Cancers (by system) This is a table showing opportunistic infections and cancers by system. | System | Examples | |---|---| | Skin | Varicella zoster, Herpes virus, Kaposi sarcoma (associated with HHV-8) | | Respiratory | PCP (Pneumocystis jirovecci pneumonia), Tuberculosis, Severe Bacterial pneumonia, Kaposi sarcoma | | GIT | Cryptosporidiosis, Candidiasis, Isosporiasis, Kaposi sarcoma, Cytomegalovirus| | CNS | Cytomegalovirus (CMV) infection, Herpes simplex (HSV) encephalitis, Toxoplasmosis, Cryptococcosis, Severe bacterial meningitis, Non-Hodgkins Lymphoma (NHL) | ## Opportunistic Tumours - Kaposi's sarcoma - Lymphomas - Cervical Cancer* ## Kaposi's Sarcoma - This is a photograph showing the characteristic skin lesions of Kaposi's sarcoma. - This is a photograph showing Kaposi's sarcoma lesions in the mouth. - This is a phtograph showing oral thrush, a common opportunistic infection in people with AIDS. ## HIV Testing Purpose of HIV testing - Diagnosis - Surveillance - Blood and organ transfusion - Travelling ## HIV Tests - Antibody Tests - Antigen tests - Nucleic acid tests ## Serological Tests 1. Rapid HIV testing - Initial Screening 2. ELISA - Confirmation test 3. Western Blot Analysis - Confirmation Test (rarely used nowadays) 4. p24 antigen - Detection of a recent infection ## HIV Antibody Rapid Test - This is a photograph showing a rapid HIV antibody test. ## ELISA for HIV Antibody - This is a photograph showing an ELISA plate used for HIV antibody testing. ## Nucleic Acid Detection - Detection of HIV viral genome through PCR - HIV RNA PCR can be: - 1. Qualitative – HIV PCR to detect presence of infection - 2. Quantitative – HIV PCR to measure viral load - HIV PCR is appropriate for infants < 18 months ## Classes Of ARVs 1. Nucleoside Reverse Transcriptase Inhibitors (NRTIs): - Zidovudine, Lamivudine, Abacavir, Tenofovir* 2. Non-Nucleoside RT Inhibitors - Nevirapine, Efavirenz, Etravirine, Delavirdine 3. Protease Inhibitors - Lopinavir, Ritonavir, Atazanavir, etc. 4. Integrase Inhibitors - Raltegravir, Dolutegravir, Elvitegravir 5. Attachment inhibitor: Maraviroc 6. Fusion Inhibitor: Enfurvirtide ## Prevention Targets - GLOBAL: 90-90-90 by 2020 - WHO: Universal Testing & Treatment (UTT) - ULTIMATE: Eradicate HIV ## Control & Prevention - Safer Sex practices - Screening (blood & blood products, organ donors) - Prevention of Mother to Child Transmission (MTCT) - Early testing and linkage with care - Treatment for prevention - Voluntary Male Medical Circumcision (VMMC) - Post-exposure prophylaxis (PEP) - Pre-exposure prophylaxis (PreP) - ?? Vaccines (Research in progress) ## Bone Marrow Transplant??? - The Berlin Patient: Timpthy Brown - London patient: Adam Castillejo - Chicago patient