HIV/AIDS and Related Infections

HIV Basics & Transmission - Viral Villainy Unveiled

• Structure: Enveloped RNA retrovirus.
  • Key Antigens: gp120 (surface, CD4 binding), gp41 (transmembrane, fusion), p24 (capsid, early marker).
• Transmission Routes:
  • Sexual (most common): Risk: receptive anal > vaginal > insertive > oral.
  • Parenteral: IV drug use (shared needles), contaminated blood products (highest efficiency).
  • Perinatal (Vertical): Mother-to-child (in utero, delivery, breastfeeding). Risk ~25-30% without ART.
• Brief Lifecycle:
  1. Attachment (gp120 to CD4+coreceptor) & Fusion (gp41).
  2. Reverse Transcription (RNA→DNA).
  3. Integration (viral DNA into host DNA).
  4. Replication, Assembly, Budding, Maturation.

⭐ p24 antigen is the earliest detectable viral marker, typically 2-3 weeks post-exposure, before antibodies develop.

Pathogenesis & Clinical Course - Immune System Under Siege

• CD4+ T-cell Depletion: HIV targets CD4+ cells, causing immune destruction. Entry via co-receptors CCR5 (early) or CXCR4 (late, faster progression).
• Infection Phases:
  1. Acute Retroviral Syndrome (ARS): 2-4 weeks post-exposure. Flu/mono-like symptoms (fever, rash). High viral load.

     ⭐ The typical 'seroconversion illness' mimics infectious mononucleosis.

  2. Clinical Latency: Asymptomatic (median ~10 yrs untreated). Gradual CD4↓.
  3. Symptomatic Disease: Constitutional symptoms, opportunistic infections (OIs).
  4. AIDS: CD4 < 200/µL OR AIDS-defining illness.

• WHO Staging (Simplified):
  • Stage 1: Asymptomatic.
  • Stage 2: Mild (e.g., weight loss <10%).
  • Stage 3: Advanced (e.g., TB, severe infections).
  • Stage 4: Severe/AIDS-defining (e.g., PCP, Kaposi).

HIV Diagnosis & ART - Finding & Fighting HIV

• Diagnosis:
  • Screening: 4th gen ELISA/Rapid (p24 Ag+Ab). Window: 2-4 wks.
  • Confirmatory: Western Blot/NAAT/HIV-RNA.
  • Infant (<18m): HIV DNA/RNA PCR (6wks, 3-6m, 12-18m).
• Monitoring: CD4 (Q3-6M), VL (at 6m, then annually if suppressed).
• ART - Treat All:
  • Goals: Suppress VL, ↑CD4, ↓transmission.
  • ⭐ > NACO 1st line: Tenofovir (TDF) + Lamivudine (3TC) + Dolutegravir (DTG).
  • 2nd line: Per resistance testing.
• ARV Classes (📌 INSTI-gravir):
  • NRTI: TDF (nephrotoxic), Zidovudine (AZT - anemia).
  • NNRTI: Efavirenz (EFV - neuropsych), Nevirapine (NVP - rash).
  • PI: Atazanavir (ATV - jaundice), Lopinavir/r (LPV/r - dyslipidemia).
  • INSTI: Dolutegravir (DTG - insomnia).
  • EI (Entry Inhibitors): Enfuvirtide.
• Prophylaxis:
  • PEP: Start <72h (TDF+3TC+DTG for 28d).
  • PrEP: Daily TDF+FTC/3TC for high-risk individuals.

Opportunistic Infections & Cancers - AIDS' Deadly Allies

Key OIs and malignancies that define AIDS, driven by severe immunosuppression. Early ART is crucial.

• Common Opportunistic Infections (Typical CD4, Dx, Tx):

  • Pneumocystis jirovecii Pneumonia (PJP): <200/µL. Dx: CXR (diffuse infiltrates), BAL. Tx: Co-trimoxazole.
  • Tuberculosis (TB): Any CD4. Dx: Sputum AFB/GeneXpert. Tx: Standard RIPE + ART.
  • Mycobacterium Avium Complex (MAC): <50/µL. Dx: Blood culture. Tx: Clarithromycin + Ethambutol.
  • Cryptococcal Meningitis: <100/µL. Dx: CSF India ink, Cryptococcal Ag. Tx: Amphotericin B + Flucytosine, then Fluconazole.
  • Cerebral Toxoplasmosis: <100/µL (if Toxo IgG positive). Dx: CT/MRI (ring-enhancing lesions). Tx: Pyrimethamine + Sulfadiazine + Leucovorin.
  • Progressive Multifocal Leukoencephalopathy (PML): <200/µL (JC virus). Dx: CSF JC virus PCR, MRI. Tx: ART.
  • CMV Retinitis: <50/µL. Dx: Fundoscopy. Tx: Ganciclovir/Valganciclovir.

• OI Prophylaxis (Primary):

  • PJP: Co-trimoxazole if CD4 <200/µL.
  • Toxoplasmosis: Co-trimoxazole if CD4 <100/µL & Toxo IgG positive.
  • MAC: Azithromycin if CD4 <50/µL.

• Common HIV-Associated Malignancies:

  • Kaposi's Sarcoma (KS) - HHV-8 associated.
  • Non-Hodgkin's Lymphoma (NHL) - esp. Primary CNS Lymphoma (EBV).
  • Cervical Cancer (invasive) - HPV associated.

• IRIS (Immune Reconstitution Inflammatory Syndrome): Paradoxical worsening of pre-existing (often subclinical) OIs after ART initiation due to recovering immunity.

⭐ Drug of choice for PCP treatment is Co-trimoxazole; also used for prophylaxis against PCP and Toxoplasmosis.

High‑Yield Points - ⚡ Biggest Takeaways

• CD4 count guides HIV staging and OI prophylaxis.
• ART is key for viral suppression and improved prognosis.
• Key OIs: PJP (CD4 < 200), Toxoplasmosis (CD4 < 100), MAC (CD4 < 50).
• IRIS (Immune Reconstitution Inflammatory Syndrome) can occur post-ART initiation.
• PEP for HIV: start ideally <2h, up to 72h post-exposure.
• HIV diagnosis: Screening tests (ELISA/Rapid) confirmed by Western Blot/NAAT.
• Prevent vertical transmission with maternal ART and neonatal prophylaxis.