HIV

  1. Discuss the epidemiology of HIV

  2. Identify sources of HIV transmission and methods for prevention

  3. Identify patients who should be screen for HIV

  4. Describe the HIV life cycle and identify current targets of antiretroviral therapy

  5. Describe the pathogenesis, diagnosis, and course of HIV infection

  6. Identify complications associated with HIV including opportunistic infections

  7. Identify candidates for antiretroviral therapy and opportunistic infection chemoprophylaxis

  1. What is the first ARV that was FDA approved?

    • Zidovudine (AZT)

  2. What population was 2/3 of new HIV diagnoses in 2022?

    • Black and Hispanic people

  3. Although HIV transmission has gone down, what age group has an increasing incidence rate?

    • 25-34 and 35-44

  4. Although HIV transmission has gone down, what race/ethnic groups has an increasing incidence rate?

    • American Indian/Alaska Native, Hisptanic/Latino and Native Hawaiiain and other Pacific Islander

  5. What treatment should all HIV infected patient receive?

    • Antiretroviral Therapy (ART)

  6. What is Antiretroviral Therapy used for?

    • Reduce morbidity & mortality and prevent transmission of HIV

  7. When should patients infected with HIV start on ART?

    • immediately after HIV diagnosis to increase the uptake of ART and linkage to care, decrease viral suppression time for individual patients, and improve virologic suppression rate

  8. What 4 studies combine results found zero HIV transmission where the HIV infected partner had durable suppression.

    • HPTN-052, Opposites Attract, Partners 1 & 2

  9. List the HIV care continuum

    • Diagnosed with HIV → Linked to Care → Receipt to Care → Retained in Care → Viral Suppression

  10. What is PreExposure Prophylaxis (PrEP)?

    • Antiretroviral therapy that’s given to prevent infection before potential exposure

  11. What is Post Exposure Prophylaxis (PEP)

    • Antiretroviral therapy that’s given within 72 hours of exposure to reduce the risk of infection

  12. Describe the regimen required for PEP

    • 3 ARVs daily for 28 days

  13. What are the 3 main transmission routes

    • Sexual, Parenteral, Mother-to-Child

  14. Describe how sexual contact is a vehicle for transmission.

    • Blood, Semen, and Vaginal Secretion

  15. Describe how parenteral is a vehicle for transmission.

    • Sharing needles/syringes, Infected blood transfusion products, Accidental contact of sharp object trauma

  16. Describe how mother to child is a vehicle for transmission.

    • Vertical transmission and Breastfeeding

  17. What transmission route is the most common?

    • sexual contact

  18. What are factors that increase the risk of transmission for sexual contact?

    • Concurrent STDs (ulcerative lesions), More infectious partner (higher viral load), Lack of male circumcision, Vaginal bleeding

  19. What are preventative measures for sexual contact transmission?

    • Abstinence, Monogamy, Barrier precautions, Reduction of high-risk behaviors, ART, PrEP, PEP

  20. What are factors that increase the risk of Parenteral transmission?

    • Exposure to contaminated blood, Intravenous Drug Use (IVDU) (used/contaminated needles), Blood transfusions, Transplanted organs, Mucocutaneous exposure (eyes, mouth, nose), Percutaneous needle stick

  21. What are preventative measures for parenteral transmission?

    • substance use treatment programs, needle exchange programs, sterilization of drug paraphernalia, PrEP, Receipt of contaminated blood products

  22. What are factors that increase the risk of mother-to-child transmission?

    • during/near time of birth, prolonged rupture of membranes, genital infection during pregnancy, preterm delivery, vaginal delivery, birth weight < 2500 gm, illicit drug use during pregnancy, HIV maternal viral load

  23. According to USPSTF, what population should be recommended to be screened for HIV?

    • 15-65, those outside the range with an increased risk, and all pregnant persons

  24. How often of those with known risk be screened?

    • annually

  25. Explain the HIV life cycle between days 0-2.

    • Exposure to HIV, Virus collected by dendritic cells and carried to lymph nodes

  26. Explain the HIV life cycle on day 3

    • HIV replicates in CD4 cells, released into blood, and spread to other organs

  27. Explain HIV life cycle after day 3

    • Continued viral replication → massive CD4 T-cell destruction → viral spread to multiple organs (brain, spleen, regional & distal lymph nodes, bone marrow)

  28. What are the targets of HIV infection and why?

    • CD4 T Helper Lymphocytes (TH1, TH2, TH17) activate macrophages, stimulate B-cell made Abs, recruit neutrophils for infection sites, regulate and limit immune response to prevent autoimmune responses

  29. Describe the HIV virus components

    • Capsid

      • HIV’s core that contains HIV RNA

    • Envelop

      • Outer surface

    • Enzymes

      • Proteins that carry out steps in HIV life cycle

    • Glycoproteins

      • Protein spikes embedded in the Envelope which attach and fuse with CD4 cells

    • RNA

      • Genetic material

  30. List the steps of the HIV life cycle

    1. Binding/Attachment

    2. Fusion

    3. Reverse Transcription

    4. Integration

    5. Replication

    6. Assembly

    7. Budding

  31. Explain Step 1: Binding

    • HIV binds to CD4+ → binds to co-receptor

  32. What HIV therapy drugs are seen targeting in the binding step?

    • Enfuvirtide, Fostemsavir, Ibalizumab, Maraviroc

  33. Explain Step 2: Fusion

    • after binding to the co-receptor the HIV envelope fuses with the CD4 cell membrane → spills viral contents into the cell (HIV RNA and Viral Enzymes — Reverse Transcriptase, Integrase, and Protease)

  34. Explain Step 3: Reverse Transcription of HIV RNA

    • Reverse Transcriptase converts HIV RNA → HIV DNA which enters the CD4 nucleus and combine with cellular DNA

  35. What HIV therapy drugs target Step 3 of Reverse Transcriptase

    • Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

      • Tenofovir, Abacavir, Emtricitabine, Lamivudine

    • Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

      • Rilpivirine, Doravirine, Efavirenz

  36. Explain Step 4: Integration of Viral DNA into Host DNA

    • Integrase joins viral and host DNA

  37. What HIV therapy drugs target (Integrase inhibitors) Step 4 of Integration

    • Dolutegravir, Bictegravir, Raltegravir, Elvitegravir, Cabotegravir

  38. Explain Step 5: Replication

    • Host begins to create long chains of HIV proteins which are building blocks for more HIV viruses

  39. Explain Step 6: Assembly

    • New HIV RNA and HIV proteins made by the host CD4 cell move to the cell surface a d assemble into immature (noninfectious) HIV

  40. Explain Step 7: Budding

    • Immature HIV virus pushed out from host CD4 cell and the long protein chains is cleaved by viral Protease

    • Protein chains form new functional HIV proteins → mature virus

  41. What HIV therapy drugs (Protease inhibitors) target Step 7 for budding?

    • Darunavir

    • Atazanavir

  42. Explain the typical course of HIV infection

    • after initial infection (acute HIV syndrome) → spiked viral load with a drop in CD4 count

    • after some weeks, CD4 begin to recover and the body starts to build immunity → drop in viral load (clinical latency period — can be years)

    • rise in viral load and sinking CD4 count until progression to AIDs or immunodeficiency syndrome

  43. What is Acute HIV Syndrome?

    • when HIV enters the body and infects a large number of CD4+ cells

    • due to high viral load, patients are high risk of transmitting

  44. What symptoms are seen during Acute HIV Syndrome?

    • Flu-like symptoms

    • Fevers, Chills, Rash, Night Sweats, Sore Throat, Fatigue, Swollen Lymph Nodes, Mouth Ulcers

  45. When do symptoms begin for Acute HIV Syndrome?

    • 1-4 weeks pose exposure and lasts ~2-4 weeks

  46. Explain the Clinical Latency period in Acute HIV Syndrome

    • begins 2-4 weeks after exposure

    • viral load falls to a set point

    • CD4 cells rebound

    • viral replication is ongoing and CD4 count will steadily decrease

  47. Explain the period that lead the Progression to AIDs

    • immune system deteriorates

    • viral load increases while CD4 count drops to dangerously low levels

    • patient at risk to develop various Opportunistic Infections (OIs)

  48. What is the median time period of typical progressors (90%)

    • 7-12 years

  49. What is the median time period of rapid progressors (<10%)

    • < 3 years

  50. What is the median time period of long term non-progressors (<1%)

    • > 15 years

    • normal, stable CD4 count and viral load of < 500 copies/mL

  51. Explain why CD4 count are markers of disease progression

    • normal: 500-1600

    • assess immunologic response to therapy

    • determines when to initiate chemoprophylaxis for OIs

    • entry into care, 3-4 months after ART initiation or change in drug therapy and periodically thereafter

  52. Explain why HIV viral load are markers of disease progression

    • # of HIV RNA copies per mL of plasma

    • each viral load test has a lower limit of detection

    • assess virologic response to therapy

    • entry into care, 2-8 months after ART initiation or change in drug therapy and every 3-4 months thereafter

    • viral load should decrease 1 log in 2-8 weeks after initiating therapy

  53. Explain the criteria for AIDs diagnosis

    • CD4 < 200 cells/mm3

    • presence of OI or AIDs defining illness

      • Oropharyngeal candidiasis

      • Cryptococcus

      • Pneumocystis pneumonia

      • Toxoplasmosis

      • Recurrent bacterial pneumonia

      • Mycobacterium avium complex

      • Kaposi’s sarcoma, other AIDs defining malignancy

      • HIV associated wasting syndrome

  54. What OI is likely to infect a patient with a CD4 cell count ~200

    • Oropharyngeal candidiasis and Pneumocystis pneumonia

  55. What OI is likely to infect a patient with a CD4 cell count ~100

    • Toxoplasmosis encephalitis and Cryptococcus meningitis

  56. What OI is likely to infect a patient with a CD4 cell count ~50

    • Mycobacterium avium complex and Cytomegalovirus retinitis

  57. What are the diagnostic tests for HIV

    • Antibody test (EIA)

      • detects HIV Abs

      • Rapid HIV screens

      • ~23-90 days after exposure

    • Antigen/Antibody Test

      • most common in labs

      • ~18-45 days after exposure

    • Nucleic Acid test

      • viral load testing

      • ~10 days after exposure