Skip to content
approvedImmune & Inflammation

Enfuvirtide

Also known as: Fuzeon, T-20, DP-178, Pentafuside

Enfuvirtide (Fuzeon) is a 36-amino acid synthetic peptide that was the first HIV fusion inhibitor approved by the FDA (2003). It works by binding to the HR1 region of the HIV-1 gp41 transmembrane protein, preventing the conformational change required for viral-host cell membrane fusion. Reserved for treatment-experienced patients with multidrug-resistant HIV-1, enfuvirtide represented a novel mechanism of action in antiretroviral therapy and demonstrated that peptide drugs could effectively treat viral infections.

3 cited references·5 researched benefits

Quick Answer

Enfuvirtide (Fuzeon) is a 36-amino acid injectable peptide and the first FDA-approved HIV fusion inhibitor (2003). It blocks HIV-1 entry into CD4+ T-cells by binding to the gp41 transmembrane protein, preventing viral-host cell membrane fusion. Reserved for treatment-experienced patients with multidrug-resistant HIV, it reduces viral load by approximately 1 log10 when added to optimized background therapy. Its twice-daily subcutaneous injections and injection-site reactions limit broader use.

Key Facts

Mechanism
Enfuvirtide mimics a portion of the HR2 (heptad repeat 2) region of HIV-1 gp41. During viral entry, HIV gp120 binds CD4 and a coreceptor (CCR5 or CXCR4), triggering a conformational change in gp41 that exposes the HR1 coiled-coil. Enfuvirtide competitively binds to HR1, blocking the interaction between HR1 and HR2 that is essential for forming the six-helix bundle structure required for viral-cell membrane fusion. By interrupting this fusion process, enfuvirtide prevents HIV-1 from injecting its genetic material into the host CD4+ T-cell. This extracellular mechanism is distinct from all other antiretroviral classes.
Research Status
approved
Half-Life
~3.8 hours
Molecular Formula
C₂₀₄H₃₀₁N₅₁O₆₄
Primary Use
Immune & Inflammation
Table of Contents

Benefits

  • Novel mechanism of action — blocks HIV entry at the fusion step, effective against viruses resistant to other antiretroviral classesstrong
  • Viral load reduction of ~1 log10 copies/mL when added to optimized background therapy in treatment-experienced patientsstrong
  • No cross-resistance with NRTIs, NNRTIs, protease inhibitors, or integrase inhibitors due to unique mechanismstrong
  • CD4+ T-cell count increase of 71–91 cells/μL at 24 weeks in TORO trialsstrong
  • Proof of concept for peptide-based antiviral therapy, inspiring development of next-generation fusion inhibitorsmoderate

Dosage Protocols

RouteDosage RangeFrequencyNotes
Subcutaneous injection90 mg (adults)Twice dailyInject into upper arm, anterior thigh, or abdomen. Rotate injection sites to reduce injection-site reactions. Must be used in combination with other antiretroviral agents, never as monotherapy.
Subcutaneous injection (pediatric)2 mg/kg (max 90 mg)Twice dailyFor patients aged 6–16 years weighing at least 11 kg. Reconstitute lyophilized powder with sterile water.

Medical disclaimer

Dosage information is provided for educational reference only. Always follow your prescriber's instructions and consult a qualified healthcare provider before starting any peptide protocol.

Side Effects

  • Injection-site reactions — nodules, erythema, induration, pain, and pruritus occur in ~98% of patientscommon
  • Diarrhea, nausea, and fatiguecommon
  • Insomnia and headachecommon
  • Hypersensitivity reactions — rash, fever, and rarely systemic reactions including hypotension and respiratory distressserious
  • Increased rate of bacterial pneumonia observed in clinical trials (mechanism unclear)serious

Frequently Asked Questions

Why is enfuvirtide not used as first-line HIV treatment?
Enfuvirtide requires twice-daily subcutaneous injections and causes injection-site reactions in nearly all patients, making it far less convenient than oral antiretrovirals. Modern first-line HIV regimens use oral combination tablets (integrase inhibitors + NRTIs) that are taken once daily with minimal side effects. Enfuvirtide is reserved for treatment-experienced patients with multidrug-resistant HIV who have limited oral options. Its high cost (historically ~$25,000/year) further limits first-line use.
How does HIV develop resistance to enfuvirtide?
Resistance to enfuvirtide develops through mutations in the HR1 region of the gp41 gene, specifically at positions 36–45. These mutations reduce binding affinity between enfuvirtide and the HR1 coiled-coil. Resistance can develop relatively quickly (within months) when enfuvirtide is used with a weak background regimen. The most common resistance mutations are G36D, V38A, V38M, Q40H, N42T, and N43D. For this reason, enfuvirtide should always be combined with at least one other active antiretroviral agent.
Is enfuvirtide still available and used?
Yes, enfuvirtide (Fuzeon) remains FDA-approved and commercially available, but its use has declined dramatically with the introduction of newer antiretroviral classes including integrase inhibitors (dolutegravir, bictegravir), second-generation NNRTIs (doravirine), and attachment inhibitors (fostemsavir). These newer agents are oral, well-tolerated, and effective against resistant virus. Enfuvirtide is now used only in rare cases where patients have exhausted virtually all other options.

References

  1. 1
    Enfuvirtide, an HIV-1 fusion inhibitor, for drug-resistant HIV infection in North and South America (TORO 1)(2003)PubMed ↗
  2. 2
    Enfuvirtide: the first fusion inhibitor for the treatment of HIV infection(2004)PubMed ↗
  3. 3
    Long-term efficacy and safety of enfuvirtide in antiretroviral-experienced patients: pooled analysis of TORO 1 and 2(2007)PubMed ↗

Latest Research

Last updated: 2026-02-19