Enfuvirtide is a 36-amino-acid synthetic peptide (MW ~4492 g/mol) that inhibits HIV-1 entry into host cells by blocking the fusion of viral and cellular membranes. It was FDA-approved in March 2003 (Fuzeon), making it the first HIV fusion inhibitor approved for clinical use. Enfuvirtide is indicated for treatment-experienced patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy, and is administered as a twice-daily subcutaneous injection.
Category: Antiviral / HIV. Evidence rating: A (strong human clinical data).
Clinical status: FDA-approved (Fuzeon for HIV-1 infection in treatment-experienced patients, March 2003)
Enfuvirtide mimics the heptad repeat 2 (HR2) region of the HIV-1 gp41 transmembrane glycoprotein. During HIV entry, the viral gp120 protein binds to CD4 and a coreceptor (CCR5 or CXCR4), triggering a conformational change in gp41 that exposes the heptad repeat 1 (HR1) coiled-coil. Enfuvirtide…
Safety considerations: Very common (>90%): injection site reactions (pain, erythema, induration, nodules, cysts, pruritus, ecchymosis) — the most significant tolerability limitation; most reactions are mild-moderate but can affect adherence; Common (>=5%): diarrhea, nausea, fatigue, insomnia, peripheral neuropathy, decreased appetite; Hypersensitivity reactions: reported in <1% of patients; may include rash, fever, nausea, vomiting, hypotension, elevated liver transaminases; rechallenge not recommended.
Reviewed by the PeptideAtlas Editorial Team.
| Molecular weight | ~4492 g/mol |
|---|---|
| CAS number | 159519-65-0 |
| Half-life | ~3.8 hours (subcutaneous) |
| Bioavailability | ~84% subcutaneous |
| Production method | synthetic |
| Anti-doping status | not-listed |
| US regulatory status | FDA-approved (Fuzeon, March 2003) for HIV-1 infection in combination with other antiretrovirals in treatment-experienced patients. |
With the development of newer antiretroviral classes (integrase inhibitors like dolutegravir, CCR5 antagonists) that are oral and better tolerated, enfuvirtide is now reserved as a last-line salvage option. The requirement for twice-daily subcutaneous injections and near-universal injection site reactions limit its long-term tolerability.
Resistance occurs through mutations in the HR1 region of gp41, particularly at amino acid positions 36-45 (GIV domain). Resistance develops rapidly with monotherapy, so enfuvirtide must always be combined with other active antiretrovirals.
Yes, Fuzeon remains available for patients who need it as a salvage regimen component. However, its use has declined substantially since approval of newer oral agents with better tolerability profiles.
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