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Updated: Feb 28 2019

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
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