Fusion Inhibitors

Snapshot

  • A 55-year-old man presents to the HIV clinic for a follow-up visit. He was recently diagnosed with HIV and was started on first-line highly active antiretroviral therapy (HAART). However, his CD4 count at his last visit remained low. Drug resistance analysis of the HIV strain was sent at that time and revealed 3 major mutations causing the virus to be resistant to many first-line agents. The analysis also revealed that the HIV strain was CCR5-tropic. The patient was started on maraviroc.

Introduction

  • Drugs
    • enfuvirtide
      • prevents penetration of HIV into CD4+ T-cells
    • maraviroc
      • prevents attachment of HIV into CD4+ T-cells
  • Clinical use
    • a class of highly active antiretroviral therapy (HAART)
  • often used as second-line in patients with drug resistance to first-line agents

Enfuvirtide

  • Mechanism of action 
    • binds to gp41, which inhibits HIV entry into the cell
  • Adverse effects
    • injection site skin reaction
    • gastrointestinal upset
  • fatigue

Maraviroc

  • Mechanism of action 
    • binds to CCR5, which is a protein on the surface of T-cells and monocytes
    • inhibits the interaction of CCR5 with gp120 on HIV, thus inhibiting docking
  • Clinical use
    • requires assay showing that the virus is CCR5-tropic, which indicates that the virus is infecting cells with CCR5 expression (vs CXCR4), making it susceptible to the drug
  • Adverse effects
    • rash
    • gastrointestinal upset
    • immunosuppression