Enfuvirtide, the First Fusion Inhibitor to Treat HIV Infection
Eva Poveda 1, Verónica Briz 1, Vicente Soriano 2
1 NULL; 2 UNIR Health Sciences School and Medical Center, Universidad Internacional de La Rioja, Madrid, Spain
*Correspondence: Eva Poveda, Email not available
Abstract
Entry inhibitors are a new class of drugs for the treatment of HIV infection. Enfuvirtide is the firstcompound of this family to be approved for clinical use. It blocks HIV fusion to host cells. It is asynthetic peptide that mimics an HR2 fragment of gp41, blocking the formation of a six-helix bundlestructure which is critical in the fusion process. Enfuvirtide is a good therapeutic option as rescuetherapy in combination with other active antiretrovirals and works against different HIV-1 variants,including all group M subtypes and group O. However, it is not active against HIV-2. The main mechanismof resistance to enfuvirtide depends of the selection of changes in a 10-amino acid domainbetween residues 36 to 45 in the HR1 region of gp41. Single and double mutations in this regionhave been shown to result in high-level resistance to enfuvirtide. A negative impact of enfuvirtideresistancemutations on viral fitness has been postulated, since resistance mutations tend to disappearsoon after drug discontinuation and because immunologic benefits have been noticed despitevirologic failure in patients undergoing enfuvirtide treatment.
