Enfuvirtide
Also known as: Fuzeon, T-20, T20, pentafuside, GP41 fusion inhibitor, DP-178
HIV-1 fusion inhibitor; synthetic peptide antiretroviral; entry inhibitor
What it is
Enfuvirtide (Fuzeon, T-20) is the only FDA-approved peptide-based HIV medication — a twice-daily injection used by people with HIV who have developed resistance to standard antiretroviral drugs. It stops the virus from entering immune cells by blocking the 'zipper' mechanism HIV uses to fuse with cells. Approved in 2003.
The scientific side
Enfuvirtide is described as a 36-amino acid synthetic peptide that mimics the heptad repeat 2 (HR2) region of the HIV-1 envelope glycoprotein gp41. HIV-1 entry into host CD4+ T cells requires a multi-step conformational change in the viral gp41 protein: after the gp120 subunit binds to the CD4 receptor, gp41 undergoes a structural transition in which the HR1 (heptad repeat 1) and HR2 (heptad repeat 2) regions fold together into a six-helix bundle (6-HB), driving the viral and cellular membranes into proximity and enabling fusion. Enfuvirtide competitively occupies the HR1 groove on gp41 by mimicking the HR2 domain, preventing formation of the 6-HB and thereby blocking membrane fusion entirely. Because enfuvirtide acts extracellularly — before the virus penetrates the host cell — it operates at a mechanistically distinct step from all other antiretroviral drug classes (reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors), conferring complete lack of cross-resistance to those agents. Resistance to enfuvirtide arises through mutations in the HR1 region of gp41 (codons 36–45), with single mutations producing partial resistance and double mutations producing high-level resistance. Pharmacokinetically, the drug has a volume of distribution of approximately 5.48 L, approximately 92% plasma protein binding, and an elimination half-life of approximately 3.8 hours; it is catabolized by tissue peptidases and proteinases. Standard adult dosing is 90 mg subcutaneously twice daily; pediatric dosing is 2 mg/kg subcutaneously twice daily. In the pivotal TORO 1 and TORO 2 trials, enfuvirtide combined with optimized background therapy produced mean HIV-1 RNA reductions of −1.48 log₁₀ copies/mL at 48 weeks versus −0.63 log₁₀ in controls (p<0.001), with mean CD4+ cell count increases of 91 cells/mm³ versus 45 cells/mm³ (p<0.001). (PMIDs: 17593608, 15110129, 14664654, 20977403, 15794736, 15031735)
Class: HIV-1 fusion inhibitor; synthetic peptide antiretroviral; entry inhibitor
Administration & storage
- Administration
- Subcutaneous injection only — not for intravenous or intramuscular useInjection sites: upper arm (triceps)anterior thighor abdomen (avoid navel and scar tissue)Rotate injection sites systematically to minimize cumulative injection site reactionsEach vial is for single use only; discard unused portionIf not injected immediately after reconstitutionstore reconstituted solution refrigerated at 2–8°C and use within 24 hours
- Storage
- Unreconstituted vials: store at room temperature 15–30°C (59–86°F). Reconstituted solution: refrigerate at 2–8°C; use within 24 hours. Do not freeze reconstituted solution. Convenience kit (vials + prefilled diluent syringes) should be stored per label instructions.
- Cautions
- Injection site reactions (ISRs) occur in approximately 98% of patients — erythema, induration, nodules/cysts, ecchymosis, pruritus — usually mild to moderate; site rotation and warm compresses help manage,Increased risk of bacterial pneumonia observed in TORO trials: pneumonia incidence 6.7 per 100 patient-years (enfuvirtide) vs. 0.6 per 100 patient-years (control); patients should seek prompt evaluation for respiratory symptoms,Hypersensitivity reactions reported in <1% of patients — may include rash, fever, nausea/vomiting, chills, rigors, hypotension, elevated liver enzymes; if systemic hypersensitivity occurs, do not rechallenge,Immune reconstitution inflammatory syndrome (IRIS) may occur when initiating antiretroviral therapy in patients with advanced HIV; monitor for inflammatory responses to previously subclinical opportunistic infections,No significant CYP450 drug interactions — enfuvirtide does not inhibit CYP1A2, 2C9, 2C19, 2D6, or 3A4; low drug interaction potential compared with most antiretrovirals,Cutaneous amyloidosis is a rare but documented adverse effect with chronic enfuvirtide use at injection sites,Cost and injection burden are practical barriers; twice-daily SC injections represent significant adherence challenge; patient education programs (e.g., TOUCH program) are critical for adherence
Legal & regulatory status
FDA-approved (NDA 021481) as Fuzeon (enfuvirtide) 90 mg/mL powder for subcutaneous injection. Approved March 13, 2003, for treatment of HIV-1 infection in treatment-experienced adults and pediatric patients (≥6 years)…
Enfuvirtide is not listed on the WADA Prohibited List. It is a prescription antiretroviral medication indicated exclusively for treating HIV-1 infection and has no known performance-enhancing application in competitive…
Approved by Health Canada as Fuzeon (enfuvirtide) for HIV-1 infection in treatment-experienced patients with ongoing viral replication. Licensed for use in combination with other antiretroviral agents. Marketed by…
What it's studied for
- Treatment of HIV-1 infection in treatment-experienced adults — virologic suppression Phase III RCT (Pivotal — FDA registration)
- Salvage therapy in heavily treatment-experienced patients with multidrug-resistant HIV-1 Phase III RCT + prognostic analysis
- HIV-1 entry inhibition in pediatric patients Clinical evidence (pediatric dosing established)
- Proof-of-concept for peptide-based HIV entry inhibition as a drug class Phase II RCT + mechanistic studies
- Resistance characterization and management in gp41 HR1 mutant HIV-1 strains Clinical resistance studies
Safety signals
- Injection site reactions (ISRs)
- Increased bacterial pneumonia risk
- Hypersensitivity reactions
- Cutaneous amyloidosis at injection sites
- Peripheral neuropathy
- Absence of hepatotoxicity
Contraindications
About these dose ranges
Dose ranges below reflect commonly reported community protocols. Where published research cites a specific dose, the PMID is linked. Doses without citations are not clinical recommendations — they reflect what practitioners and researchers commonly report using.
Community-reported dosing
| Route | Dose | Frequency / Duration | Population / context | Source tier |
|---|---|---|---|---|
| Unspecified | 90 mg per injection | — | Adults with HIV-1 infection (FDA-approved) | Research |
| Unspecified | 2 mg/kg per injection (maximum 90 mg) | — | Pediatric patients aged ≥6 years (FDA-approved) | Research |
| Unspecified | 90 mg per injection | — | Treatment-experienced adults in TORO trials | Research |
| subcutaneous injection | 90 mg per injection (adults); 2 mg/kg per injection (pediatric ≥6 years, max 90 mg) | twice daily (every 12 hours) | HIV-1-infected adults with documented treatment failure and multidrug-resistant virus on antiretroviral therapy |