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HIV Disease

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Summary

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Key Points

  • HIV: Disease
    • Transmission
      • Sexual intercourse
        • Responsible for >80% of transmission globally
      • Blood (e.g. sharing needles)
        • Responsible for 30% of transmission in developed countries
      • Vertical transmission (mother to fetus)
        • Responsible for >90% of childhood HIV
    • Presentation
      • 4 phases (left untreated)
        • Acute Flu-like illness
          • Occurs from 0 to 6 months after infection
          • Non-specific symptoms (fever, lymphadenopathy,  sore throat, rash, weight loss, headache, myalgia/arthralgia, mucocutaneous ulcers)
          • Viremia (rapidly increasing viral load)
          • Seeding of lymphoid organs
        • Latency phase
          • Occurs from 6 months to 10 years after infection
          • Viral load reaches steady levels
          • Virus replicates in CD4+ T-cells of lymph nodes
            • Slow, steady decline in CD4+ counts
        • Moderate immunocompromise (CD4+ <500 cells/mm3)
          • Opportunistic infections begin to occur
            • CD4+ counts fall below certain thresholds, crippling immune response
          • Skin and mucosal infections usually seen (e.g. Candida, S. aureus)
        • AIDS (CD4+ <200 cells/mm3)
          • Severe immunodeficiency characterized by either
            • CD4+ <200 cells/mm3
            • AIDS-defining illness (e.g. Pneumocystis pneumonia)
              • regardless of CD4 count
          • Severe systemic illnesses and malignancies seen
            • Cognitive decline (HIV dementia) may also be observed
    • Diagnosis
      • HIV-1/2 antibodies (IgG) AND viral p24 antigen immunoassays (ELISA)
        • Detect amounts of viral p24 Ag capsid protein and IgG Abs to HIV-½
          • Very high sensitivity/specificity for HIV
        • If negative
          • The patient is HIV-negative
            • no further testing needed
        • If positive
          • HIV-1/HIV-2 Antibody Differentiation immunoassay
            • If positive
              • Confirms HIV-positive status
              • Determines if infected with HIV-1, HIV-2, or both
            • If negative/indeterminate
              • Viral Load testing is performed
        • Not recommended in neonates with suspected HIV
          • Confounded by maternally-transferred IgG antibodies
          • HIV viral load is a better predictor in infants
      • Viral load testing
        • Also known as qRT-PCR or nucleic acid testing (NAT)
        • Determines amount of viral RNA in plasma
          • Higher viral load →  poor prognosis
          • Used to assess treatment response to antiretroviral agents
      • CD4+ T-cell count/percentage
        • Determines stage/severity of disease (AIDS status)
        • May be used to monitor treatment response
      • Western blot tests no longer recommended by CDC for confirmatory testing
    • Treatment
      • HIV genotyping/drug resistance testing determines which antiretrovirals are used
      • HIV undergoes many mutations, which accelerate in the context of HAART
        • Multiple simultaneous drugs reduce development of resistance
        • Many different agents of each class developed to circumvent resistance
      • Highly Active Antiretroviral Therapy (HAART)
        • First-line treatment for all patients with HIV
        • 2 nucleoside reverse transcriptase inhibitors (e.g., tenofovir alafenamide and emtricitabine) and an integrase inhibitor (e.g., bictegravir)
        • Fat redistribution is a common side effect of HAART (associated with NRTIs and Protease inhibitors)
    • Prophylaxis
      • Pre-exposure prophylaxis (PREP)
        • Prevents HIV infection in high-risk patients
        • drug regimen
          • tenofovir and emtricitabine
      • Post-exposure prophylaxis (PEP)
        • Given immediately after HIV exposure
          • E.g. after unprotected sexual intercourse, healthcare exposure
          • initiate within 72 hours
        • drug regimen
          • tenofovir, emtricitabine, and raltegravir
          • tenofovir, emtricitabine, and dolutegravir
      • Antiretroviral therapy in HIV+ pregnant mothers
        • Generally treated the same as nonpregnant patients
          • certain medications should be avoided
            • dolutegravir
            • elvitegravir
            • tenofovir alafenamide
        • Intrapartum management
          • HIV RNA ≤ 1000 copies/mL
            • cesarean section not needed
          • HIV RNA > 1000 copies/mL
            • perform cesarean section at 38 weeks
              • prevents HIV exposure to the baby via rupture of membranes
            • intravenous zidovudine
        • Postpartum management
          • Given to all infants born to HIV-infected mothers
          • mothers with HIV RNA ≤ 1000 copies/mL
            • zidovudine in the infant for 4-6 weeks
          • mothers with HIV RNA > 1000 copies/mL
            • zidovudine, lamivudine, and nevirapine in the infant for 6 weeks