HIV fusion inhibitor · injected peptide
A synthetic peptide of 36 amino acids, enfuvirtide is an HIV-1 fusion inhibitor: it stops the virus from fusing with CD4 immune cells and getting inside them1. Developed as T-20 and marketed as Fuzeon, it was used alongside other antiretrovirals in people whose virus kept replicating despite treatment, typically after several drug classes had stopped working.
To infect a CD4 cell, HIV-1 uses its envelope protein gp41 to pull the viral and cell membranes together, which requires gp41 to change shape. Enfuvirtide copies a stretch of gp41 and binds a region of it called the first heptad repeat (HR1), blocking the shape change needed for fusion4. The membranes never merge, so the virus cannot deliver its genetic material into the cell. Because it acts outside the cell, before infection, it works by a different route than drugs aimed at viral enzymes, and in laboratory studies HIV-1 resistant to those older drug classes remained sensitive to it. It has no activity against HIV-2, and HIV-1 with reduced sensitivity to enfuvirtide has emerged both in the laboratory and in trial participants whose treatment failed4.
In a small 1998 human study, 14 days of intravenous T-20 in 16 adults with HIV produced dose-related falls in blood viral load, early proof in people that viral entry can be blocked1. Two 24-week phase 3 trials, TORO 1 in North and South America (501 randomized) and TORO 2 in Europe and Australia (512 randomized), enrolled people previously treated with, or resistant to, the three main drug classes of the time. Adding enfuvirtide to an optimized background regimen lowered viral load and raised CD4 counts more than the background regimen alone2,3.
In TORO 1, 98 percent of enfuvirtide recipients reported injection-site reactions, and pneumonia was more frequent than in the control group2. In 2024 Genentech announced it would end US distribution in February 2025, citing newer treatment options and reduced medical need, and said the decision was not related to the product's quality or effectiveness5.
The FDA approved Fuzeon in 2003 for HIV-1 infection, in combination with other antiretrovirals, in treatment-experienced patients with ongoing viral replication4. Drugs@FDA now lists it as discontinued, and Genentech ended US distribution in February 20255,6.
Per the FDA label, 98% of trial participants had at least one injection-site reaction: pain, redness, nodules or cysts, and bruising. Other common effects were diarrhea, nausea and fatigue. Warnings cover systemic allergic reactions, pneumonia, bleeding at injection sites in people on anticoagulants or with hemophilia, nerve pain with a needle-free injector, and immune reconstitution syndrome. Antibodies to enfuvirtide could in theory cause a false-positive HIV antibody test in people without HIV4.
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