Enfuvirtide: from basic investigations to current clinical use.
BACKGROUND
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.


METHODS
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'.


RESULTS
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.


CONCLUSIONS
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.
Hôpital Bichat Claude Bernard, Maladies Infectieuses, 46 rue Henri Huchard, 75877 Paris Cedex 18, France. veronique.joly@bch.aphp.fr
Véronique
V
Joly
Kaoutar
K
Jidar
Mercedes
M
Tatay
Patrick
P
Yeni
D000818:Animals; D017326:Clinical Trials, Phase III as Topic; D004347:Drug Interactions; D024882:Drug Resistance, Viral; D000077560:Enfuvirtide; D015700:HIV Envelope Protein gp41 / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D023581:HIV Fusion Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D010446:Peptide Fragments / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D016879:Salvage Therapy / Q000379:methods
D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D010446:Peptide Fragments; D000077560:Enfuvirtide