Enfuvirtide: from basic investigations to current clinical use

Importance of the field: Drug resistance is a major challenge in the treatment of HIV infection. Enfuvirtide is the first entry inhibitor to have been approved for clinical use. Areas covered in this review: Relevant information through searches of MEDLINE (1998 to June 2010) and meeting abstracts of major HIV/AIDS conferences (2003 - June 2010) using the search terms 'enfuvirtide', 'T-20' and 'fusion inhibitor'. What the reader will gain: Enfuvirtide blocks HIV fusion to host cells. It works against the different HIV-1 variants but is not active against HIV-2. The recommended dosage of enfuvirtide is 90 mg b.i.d. subcutaneously. The two large Phase III pivotal clinical trials TORO 1 and 2 showed that enfuvirtide is an effective therapeutic option as rescue therapy in combination with other active antiretroviral drugs. Resistance to enfuvirtide is conferred by mutations in the HR1 region of gp41. Single and double mutations have been shown to result in high-level resistance to enfuvirtide. Postmarketing studies have been helpful to define more precisely the place of enfuvirtide in the sequence of antiretroviral therapy. Take home message: The emergence of new compounds and new classes of drugs, highly active against multiresistant virus but more convenient to administer than enfuvirtide, will probably prevent the extensive use of enfuvirtide. This drug remains attractive in some subgroups of patients because of its excellent systemic tolerance and the lack of interactions with the major cytochrome P450 isoenzymes.