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.