HIV/AIDS and Related Infections

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HIV Basics & Transmission - Viral Villainy Unveiled

  • Structure: Enveloped RNA retrovirus.
    • Key Antigens: gp120 (surface, CD4 binding), gp41 (transmembrane, fusion), p24 (capsid, early marker). HIV virus structure diagram
  • 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.

HIV natural history: CD4 count and viral load

  • 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. HIV replication cycle and drug targets
  • 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.

MRI of Toxoplasmosis in HIV/AIDS

⭐ 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.

Practice Questions: HIV/AIDS and Related Infections

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WHO AIDS defining illnesses are all EXCEPT:

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Flashcards: HIV/AIDS and Related Infections

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The prodrome (onset) of HIV consists of flu or _____-like symptoms with cervical lymphadenopathy and fever

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The prodrome (onset) of HIV consists of flu or _____-like symptoms with cervical lymphadenopathy and fever

mono

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