HIV and Retroviruses

HIV Structure & Replication - Viral Vitals & Entry

• Virus: Retroviridae (Lentivirus); 100-120 nm spherical, enveloped.

• Genome: Two identical (+)ssRNA strands.

• Key Components:

  • Envelope: gp120 (attachment), gp41 (fusion).
  • Capsid: p24 (core antigen, diagnostic).
  • Matrix: p17.
  • Enzymes: Reverse Transcriptase (RT), Integrase (IN), Protease (PR).

• Viral Entry Process:

  

  • Attachment: gp120 to CD4.
  • Co-receptor: CCR5 (M-tropic, early) or CXCR4 (T-tropic, late). 📌 R5 vs X4 tropism.
  • Fusion & Entry: gp41 facilitates membrane fusion; core released.

⭐ Key enzymes: Reverse Transcriptase, Integrase, Protease are crucial for viral replication and are major targets for Antiretroviral Therapy (ART).

HIV Pathogenesis & Clinical Course - Immune Sabotage

⭐ HIV primarily infects and destroys CD4+ T-lymphocytes, leading to progressive immune deficiency. AIDS is diagnosed when CD4 count drops below 200 cells/µL or with an AIDS-defining illness.

• Primary Targets & Entry:
  • Infects CD4+ T-cells, macrophages, dendritic cells.
  • Uses CD4 receptor & co-receptors (CCR5/CXCR4) for entry.
• Mechanisms of Immune Destruction:
  • Direct lysis of infected CD4+ cells.
  • Apoptosis of infected & bystander cells.
  • Syncytia formation (fusion of infected cells).
  • Chronic immune activation leading to T-cell exhaustion.
  • Early GALT (Gut-Associated Lymphoid Tissue) destruction.
• Clinical Course:
  • Acute Retroviral Syndrome (ARS): flu-like, high viremia.
  • Clinical Latency: asymptomatic, viral replication persists, gradual ↓CD4.
  • AIDS: CD4 < 200 cells/µL, opportunistic infections, neoplasms.

HIV Diagnosis & Lab Monitoring - Detective Work

• Screening Tests:
  • ELISA (Antibody/p24 Antigen).
  • Rapid tests (Antibody/Antigen).
• Confirmatory Tests:
  • Western Blot (WB): Detects specific HIV antibodies.
  • HIV NAAT (Nucleic Acid Amplification Test): Detects HIV RNA/DNA. Crucial for acute infection, window period, and Early Infant Diagnosis.
• Window Period: Typically 3-12 weeks post-exposure where tests may be falsely negative. 📌 "WP" - Wait Patiently.
• Monitoring Disease Progression & Treatment Response:
  • CD4+ T-cell count: Measures immune status. ART usually initiated if < 350-500 cells/µL.
  • Viral Load (HIV RNA PCR): Quantifies virus in blood. Goal: Undetectable with ART.
• Early Infant Diagnosis (EID): Virologic tests (HIV DNA/RNA PCR) by 4-6 weeks of age, as maternal antibodies interfere with antibody tests.

⭐ The standard diagnostic algorithm involves an initial ELISA/rapid test followed by a confirmatory test like Western Blot or HIV NAAT. The window period (typically 3-12 weeks) can lead to false negatives early in infection.

HIV Management & Prevention - Fighting Back

• Antiretroviral Therapy (ART)
  • Goals: Suppress viral load, restore immune function (↑CD4), reduce morbidity & mortality.
  • ⭐ > HAART (Highly Active Antiretroviral Therapy) typically combines ≥3 drugs from ≥2 classes to suppress viral replication and prevent resistance.
  • Classes: NRTIs, NNRTIs, PIs, INSTIs, Entry Inhibitors.
  • Initiate ART for all HIV+ individuals.
• Monitoring Response
  • CD4 count: Immune status (Normal: 500-1500).
  • Viral Load (HIV RNA): Treatment efficacy; goal: undetectable (<50 copies/mL).
• Opportunistic Infections (OIs) Prophylaxis
  • ⭐ > Prophylaxis for Pneumocystis jirovecii pneumonia (PJP) is indicated when CD4 count < 200 cells/µL.
    • Primary drug: TMP-SMX.
  • Toxoplasmosis (T. gondii): Prophylaxis if CD4 < 100 cells/µL (TMP-SMX).
  • MAC (M. avium complex): Prophylaxis if CD4 < 50 cells/µL (Azithromycin).
• Prevention Strategies
  • Screening, safe sex (condoms), clean needles.
  • PMTCT: Maternal ART, infant ARVs.
  • PrEP (Pre-Exposure Prophylaxis): Daily ARVs for high-risk.
  • PEP (Post-Exposure Prophylaxis): ARVs within 72 hrs post-exposure.

High‑Yield Points - ⚡ Biggest Takeaways

• Retroviruses are RNA viruses with reverse transcriptase converting RNA to DNA.
• HIV-1 is globally prevalent; HIV-2 in West Africa, slower progression.
• Key genes: gag (p24), pol (RT, integrase, protease), env (gp120, gp41).
• gp120 binds CD4 and co-receptors (CCR5/CXCR4); gp41 mediates viral fusion.
• Diagnosis: ELISA (screening), Western blot (confirmatory), NAAT (viral load, early detection).
• AIDS diagnosis: CD4 count < 200 cells/µL or specific opportunistic infections.