Enfuvirtide

Also known as: Fuzeon, T-20

Enfuvirtide (Fuzeon, T-20) is a 36-amino acid synthetic peptide that functions as a fusion inhibitor, targeting the HIV-1 envelope glycoprotein gp41. It binds to the heptad repeat 1 (HR1) region of gp41, preventing the conformational change required for fusion between the viral and host cell membranes. This blocks viral entry into CD4+ T cells, distinguishing it from other antiretroviral classes that act intracellularly. As a first-in-class fusion inhibitor, it provides a unique mechanism for suppressing HIV replication, particularly in treatment-experienced patients with multidrug-resistant virus. Key research findings from clinical trials (e.g., TORO 1 and TORO 2) demonstrated that enfuvirtide, when added to an optimized background regimen, significantly reduced viral load and increased CD4+ cell counts compared to background therapy alone. However, its use is limited by the need for twice-daily subcutaneous injections, frequent injection-site reactions, and high cost. Long-term studies confirmed sustained virologic suppression in adherent patients, though resistance mutations (e.g., in the HR1 region) can emerge, reducing efficacy. Clinically, enfuvirtide is approved for use in heavily treatment-experienced adults and children with HIV-1 who have evidence of viral replication despite ongoing antiretroviral therapy. It is reserved for salvage therapy due to its parenteral administration and tolerability issues. While newer oral agents have largely supplanted its use, enfuvirtide remains a valuable option in cases of extensive drug resistance. For research purposes only — not medical advice.

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