HIV/AIDS

HIV Pathophysiology - Viral Hijacker

• Target: CD4+ T-helper cells.
• Viral Entry: gp120 binds to CD4, then a coreceptor (CCR5/CXCR4). gp41 mediates membrane fusion.
• Replication Hijack:
  • Reverse Transcriptase: Converts viral RNA to proviral DNA.
  • Integrase: Inserts proviral DNA into the host genome.
  • Protease: Cleaves viral polyproteins for maturation.

⭐ Viral Tropism: Coreceptor use (CCR5 vs. CXCR4) is key. Early HIV favors CCR5 (M-tropic), a target for entry inhibitors like Maraviroc.

HIV Diagnosis & Staging - The Count Down

• Screening: 4th-gen combination immunoassay (p24 antigen + HIV-1/2 Abs).
• Confirmation: HIV-1/HIV-2 antibody differentiation immunoassay.
• Indeterminate? HIV-1 Nucleic Acid Test (NAT) for viral load.

Staging by CD4+ Count (cells/μL):

• Stage 1: >500
• Stage 2: 200-499
• Stage 3 (AIDS): <200 or AIDS-defining illness.

⭐ The p24 antigen is detectable before antibodies, shortening the diagnostic window period to ~2 weeks.

Opportunistic Infections - When Guards Are Down

• Risk of specific infections escalates as CD4+ T-cell counts decline. Prophylaxis is critical.
• Key Thresholds & Prophylaxis:
  • CD4 < 200 cells/mm³: Pneumocystis jirovecii pneumonia (PCP). Prophylax with TMP-SMX.
  • CD4 < 100 cells/mm³: Toxoplasma gondii, Cryptococcus neoformans. Prophylax with TMP-SMX (covers Toxo).
  • CD4 < 50 cells/mm³: Mycobacterium avium complex (MAC), CMV retinitis. Prophylax with Azithromycin for MAC.

⭐ The most common cause of seizures in an HIV-positive patient with a CD4 count < 100 is CNS toxoplasmosis.

Antiretroviral Therapy (ART) - The Drug Cocktail

ART aims to suppress HIV replication, restore immune function, and reduce transmission. The standard initial regimen is a "cocktail" of drugs to prevent resistance.

• Backbone: 2 Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs)
  • Tenofovir, Emtricitabine, Abacavir
• Core Agent: 1 Integrase Strand Transfer Inhibitor (INSTI)
  • Dolutegravir, Bictegravir, Raltegravir

⭐ U=U: Undetectable = Untransmittable. Patients with a sustained undetectable viral load (<50 copies/mL) cannot sexually transmit HIV.

Prophylaxis & PrEP - Prevention Power-Up

• CD4-Guided Prophylaxis (when to start):
  • CD4 < 200: TMP-SMX for Pneumocystis jirovecii (PCP).
  • CD4 < 100: TMP-SMX for Toxoplasmosis.
  • CD4 < 50: Azithromycin for Mycobacterium avium complex (MAC).
• PrEP (Pre-Exposure Prophylaxis):
  • Daily oral tenofovir/emtricitabine (TDF/FTC) for high-risk individuals to prevent acquisition.

⭐ PrEP reduces the risk of sexually acquired HIV by >99% when taken consistently.

High‑Yield Points - ⚡ Biggest Takeaways

• Screening with ELISA, confirmed by Western blot or HIV-1/2 differentiation assay.
• CD4+ count dictates opportunistic infection (OI) risk and guides prophylaxis.
• Key OI thresholds: PJP (<200), Toxoplasmosis (<100), MAC (<50).
• Antiretroviral therapy (ART) is recommended for all HIV-positive individuals.
• Standard of care is HAART, typically 2 NRTIs plus an integrase inhibitor.
• Watch for Immune Reconstitution Inflammatory Syndrome (IRIS) after initiating ART.