Enfuvirtide is a 36-amino-acid synthetic peptide and a prescription antiretroviral drug. It was the first member of a drug class called HIV fusion inhibitors, also known as entry inhibitors, and it carries the brand name Fuzeon. In the research literature it appears under the development codes T-20 and DP-178, and the older name pentafuside.
Most HIV drugs act after the virus has already entered a CD4 T cell. Enfuvirtide works earlier. Its sequence is copied from the C-terminal heptad repeat of gp41, the transmembrane part of the HIV-1 envelope protein. When the virus tries to fuse with a host cell, gp41 folds into a hairpin (a six-helix bundle) that pulls the viral and cell membranes together. Enfuvirtide binds the HR1 region of gp41 and gets in the way of that folding, so the membranes never merge and the virus cannot get in. This mechanism is described in the Nature Reviews Drug Discovery profile of enfuvirtide and in mechanistic work published in the Journal of Biological Chemistry.
What the clinical evidence shows
Enfuvirtide was approved by the US FDA in March 2003. It was developed by Trimeris and Roche. Approval rested on two large phase III trials, T-20 versus Optimized Regimen Only, known as TORO 1 and TORO 2, in patients with HIV that had already become resistant to other drugs.
In TORO 1, conducted in North and South America, 501 treatment-experienced patients were randomized. Adding enfuvirtide to an optimized background regimen lowered HIV-1 RNA by a mean of 1.70 log10 copies/mL at 24 weeks, compared with 0.76 log10 in the group on the optimized regimen alone. TORO 2, run in Europe and Australia and published in the New England Journal of Medicine, found a similar difference of about 0.78 log10 copies/mL in favor of enfuvirtide. The drug is given by subcutaneous injection twice daily. Injection-site reactions were near universal in the trials, reported by 98 percent of patients in TORO 1, though only about 3 percent stopped treatment because of them.
Because it has to be injected and resistance can develop, enfuvirtide is generally reserved for salvage therapy when more convenient oral regimens have failed. Newer entry inhibitors have since arrived, but enfuvirtide remains the proof of concept for blocking HIV at the fusion step.
Regulatory and anti-doping status
Enfuvirtide is an approved medicine for HIV-1 infection, used in combination with other antiretrovirals. It is not a performance-enhancing agent and is not a focus of the WADA Prohibited List. It has no recognized use outside HIV treatment.
A note on sourcing: vials sold by research-chemical suppliers are not the same thing as the pharmaceutical product. If you see enfuvirtide offered as a "research peptide," that material is sold for laboratory use only, is not approved for human consumption, and has not been through the quality controls that apply to a prescription drug. For lab-use material, a current certificate of analysis (COA) covering identity and purity by HPLC and mass spectrometry, ideally from an independent third-party lab rather than the seller, is the minimum a buyer should expect. peptideone aggregates third-party COA and vendor-rating data where it exists; it does not test products itself.
This page is informational only. It is not medical advice and not dosing guidance. Enfuvirtide is a prescription drug, and any clinical use belongs with a licensed physician.