HIV: Clinical Course

Summary

Human Immunodeficiency Virus or HIV infections are characterized by increasing immunodeficiency over time. The virus is initially transmitted in 3 ways: through sexual intercourse, blood contact, or vertical transmission from mother to child. After transmission, people infected with HIV usually experience 4 distinct phases if the disease is left untreated.

The first phase is an acute flu-like illness, where the virus rapidly replicates and infects new cells over the first 6 months after exposure.

After, there is a latency phase which can last anywhere from 6 months to 10 years, during which the virus replicates slowly in the immune cells of our body. This phase is described as latent or dormant, because patients typically experience little to no symptoms during this time.

Later in the clinical course of HIV, enough immune cells die to cause moderate immunocompromise in patients, as CD4-positive cell counts fall below 500 cells. Patients will begin getting infections more frequently.

Finally, the last stage of the disease is acquired immunodeficiency syndrome or AIDS. AIDS is a stage of severe immunocompromise which is defined as meeting one of two criteria: having an AIDS-defining illness, or a CD4-positive cell count of less than 200. In AIDS, patients experience severe infections from opportunistic pathogens, as well as various cancers and dementia.

To make a diagnosis of HIV, serum assays for both HIV antibodies and the p24 antigen are used.

The most common treatment for HIV is HAART, or Highly Active Antiretroviral Therapy, which is a combination therapy including two NRTIs and either an integrase or protease inhibitor.

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