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 s...