Enfuvirtide
HIV fusion inhibitor peptide
Also Fuzeon, T-20, T20, Pentafuside, DP-178
- Evidence
- AStrong human evidence
- FDA status
- FDA approvedas of 2026-10-26
- Route
- Injection
- Studies cited
- 1 human0 animal or cell
An HIV drug given as an injection twice a day for people whose virus resisted other drugs. Two trials showed it works, but newer drugs have replaced it.
Sold for
Enfuvirtide was the first HIV fusion inhibitor, a twice-daily injection that rescued patients whose virus had outrun every oral drug.
Studies say
Two randomized trials in multidrug-resistant HIV showed clear virologic benefit, an A for its approved use, though newer oral and long-acting drugs have made it obsolete.
Why grade A. Approval rested on two randomized open-label phase 3 trials, TORO 1 (n=501, cited here) and TORO 2, in heavily treatment-experienced patients, both showing a larger drop in viral load when enfuvirtide was added to an optimized regimen. That is an A for salvage HIV therapy; the drug has no other use. 12
FDA. Approved but discontinued. Enfuvirtide was approved by the FDA in March 2003 as Fuzeon (Roche/Genentech) for HIV-1 infection in treatment-experienced patients with ongoing viral replication despite antiretroviral therapy. Genentech discontinued Fuzeon in the US effective February 28, 2025, citing declining need; the approval stands but the product is no longer sold. 2
Written from 2 cited sources. Fact-checked 2026-10-27: 14 claims checked, 0 corrected. Last refreshed 2026-10-27. Not physician reviewed.
What this means for you
- What people take it for
- HIV that resists other drugs
- Can a US doctor prescribe it?
- Yes, FDA approved for HIV, but the maker stopped selling it in the US in 2025.
- Properly tested in people?
- Yes, in large controlled trials; one covered 501 people.
Evidence checklist
- Randomised controlled trial TORO 1 and 2, randomized open-labelyes
- Human study over 100 people TORO 1 enrolled 501yes
- More than one research group Trials run by sponsors Roche and Trimerisno
- Clinical outcomes, not surrogate markers Viral load, a surrogate markerno
- Human safety data beyond case reports Trial safety data, near-universal site reactionsyes
Drawn from the cited studies below. A dash means the sources give no information.
What it is
Enfuvirtide is a lab-made peptide of 36 amino acids. It is copied from a segment of gp41, the HIV envelope protein that drives the virus into a cell. It was the first drug to block HIV entry instead of the virus's enzymes. It was also the first antiretroviral given by injection. The peptide is long, so making it took more than 100 chemical steps. That made it one of the most expensive HIV drugs of its era. 1
Fuzeon was approved in 2003 for patients whose HIV had become resistant to multiple drug classes. Integrase inhibitors and other better-tolerated options arrived later. Its use fell to a small number of patients. Genentech withdrew it from the US market in February 2025. 2
How it works
To infect a CD4 cell, HIV's gp41 protein must fold back on itself. It forms a six-helix bundle that pulls the viral and cell membranes together. Enfuvirtide mimics one of the gp41 helices and binds the other. It jams the fold before the bundle can form. The virus stays stuck on the cell surface. The drug acts outside the cell. So it works against virus that resists reverse transcriptase, protease and integrase inhibitors. Resistance to enfuvirtide itself arises through mutations in gp41, not in those enzymes. 1
What human research shows
TORO 1 enrolled 501 patients in North America and Brazil. They had taken an average of a dozen antiretrovirals and had resistance to all three oral classes. Researchers randomized them 2:1 to an individually optimized background regimen with or without enfuvirtide. At 24 weeks, viral load fell by 1.70 log10 copies per milliliter with enfuvirtide versus 0.76 without. HIV RNA was below 400 copies in 37% of the enfuvirtide group, compared with 16% of controls. CD4 counts rose more with enfuvirtide. TORO 2, run in Europe and Australia, found the same. 1
The effect depended on the rest of the regimen. Patients who had at least two other active drugs in their background therapy did far better than those who had none. This is the general rule in salvage HIV treatment. 1
| Study | Model | Finding |
|---|---|---|
| TORO 1 | Humans, n=501, randomized open-label, 24 weeks, multidrug-resistant HIV | Adding enfuvirtide to an optimized regimen roughly doubled the drop in viral load and the share of patients below 400 copies per milliliter. 1 |
| Genentech discontinuation statement | Manufacturer notice, 2024 | Fuzeon was withdrawn from the US market effective February 28, 2025 because of reduced need as newer treatments became available. 2 |
Safety
Injection-site reactions were close to universal. In TORO 1, 98% of enfuvirtide patients had pain, redness, nodules or cysts at injection sites. About 4% stopped treatment because of them. The trials also found a higher rate of bacterial pneumonia in the enfuvirtide arm, which the label flagged. Rare hypersensitivity reactions also occurred. Diarrhea, nausea and fatigue were otherwise similar to controls. 12
Questions for your clinician
- Is enfuvirtide still obtainable now that Fuzeon has been withdrawn?
- Which newer drugs suit a person with resistant HIV?
- How are injection-site reactions managed?
Questions people ask
Is enfuvirtide FDA-approved?
The 2003 approval for treatment-experienced HIV-1 infection remains on the books. But Genentech stopped selling Fuzeon in the US on February 28, 2025. 2
Why was Fuzeon discontinued?
Demand collapsed. Integrase inhibitors, boosted protease inhibitors and long-acting injectables such as cabotegravir and lenacapavir treat resistant HIV. They do so without twice-daily injections and the near-universal injection-site reactions. Genentech cited reduced need as the reason. 2
How well did enfuvirtide work?
In TORO 1, it was added to an optimized regimen in 501 heavily treated patients. At 24 weeks, viral load dropped 1.70 log versus 0.76 without it. The benefit was largest when other active drugs were available to pair with it. 1