Understanding Anti-Retrovirals for HIV Treatment

Sep 26, 2024

Anti-Retrovirals and HIV Treatment

Overview

  • Anti-retrovirals are essential for treating HIV patients.
  • Treatment should start as soon as patients are ready, regardless of CD4 T cell count.

HIV Life Cycle Recap

  1. Targeting CD4 T Cells

    • HIV targets CD4 T cells, which are crucial immune cells.
    • Glycoprotein GP120 binds to CD4 receptors and co-receptors CCR5 and CXCR4.
    • Fusion of the viral envelope and cell membrane is facilitated by GP41.
  2. Reverse Transcription

    • The virus uses reverse transcriptase to convert its RNA into DNA.
    • Single-stranded viral RNA is transformed into double-stranded viral DNA.
  3. Integration

    • Viral DNA is integrated into the host cell DNA via integrase.
    • The virus utilizes the host's machinery to replicate.
  4. Transcription and Translation

    • Host RNA polymerase reads viral DNA to create viral RNA and mRNA.
    • Ribosomes translate mRNA to synthesize viral proteins.
  5. Assembly and Maturation

    • Newly formed viral components are packaged and released.
    • Maturation occurs, producing an infective HIV form.

Classes of Anti-Retrovirals

  1. Attachment and Entry Inhibitors

    • CD4 Binding Inhibitors: E.g., Ibalizumab prevents HIV entry.
    • CCR5 Inhibitors: E.g., Maraviroc blocks CCR5, adverse effects include hepatotoxicity and rash.
    • Fusion Inhibitors: E.g., Enfuvirtide binds to GP41 to prevent fusion; common side effects are localized skin reactions.
  2. Reverse Transcriptase Inhibitors (RTIs)

    • Nucleoside RTIs: E.g., Abacavir, Lamivudine, Zidovudine; act as chain terminators.
      • Key Points for Abacavir:
      • Causes hypersensitivity reactions; genetic testing for HLA-B5701 recommended.
      • Increases cardiovascular risk.
    • Nucleotide RTIs: E.g., Tenofovir (TDF and TAF); also chain terminators but differ in half-life and side effects.
      • TDF associated with nephrotoxicity and bone toxicity.
    • Non-Nucleoside RTIs: E.g., Efavirenz; binds directly to reverse transcriptase, causing neuropsychiatric side effects.
  3. Integrase Inhibitors

    • End with "-gravir" (e.g., Raltegravir, Dolutegravir); block integration of viral DNA into host DNA.
    • Common side effects include myopathy and elevated creatinine.
  4. Protease Inhibitors

    • End with "-navir" (e.g., Atazanavir, Darunavir); inhibit protease activity, leading to immature viruses.
    • Require booster agents like Ritonavir or Cobicistat.
    • Side effects include nausea, diarrhea, hyperlipidemia, and insulin resistance, with specific effects for each drug.

Other Treatments for HIV Patients

  • Prophylaxis for Opportunistic Infections: Vaccinations and medications like Bactrim for PJP and toxoplasmosis.
  • Latent TB Treatment: Essential for HIV patients with latent TB.

Immune Reconstitution Syndrome (IRIS)

  • Occurs a few months after starting antiretrovirals as CD4 counts rise, causing inflammation and infection symptoms.

Conclusion

  • Antiretroviral therapy should combine different classes (e.g., RTI with Integrase Inhibitor).
  • Key drug classes to remember: Reverse Transcriptase Inhibitors, Integrase Inhibitors, Protease Inhibitors.