Enfuvirtide: the first HIV fusion inhibitor.
Highly active antiretroviral therapy, a combination of antiretrovirals to treat HIV-infected individuals, may fail for a number of reasons, including the selection of genetic mutations which confer resistance to the antiretroviral drugs, and poor adherence or treatment discontinuation resulting from drug toxicity. Treatment-experienced patients, who have failed therapy owing to the emergence of drug-resistant virus, have a significant unmet medical need. Enfuvirtide (T-20), the first of a new class of antiretroviral agents known as HIV fusion inhibitors, has a unique mechanism of action involving disruption of HIV entry at the stage of membrane fusion. The potent antiviral activity and favourable safety and tolerability profile of enfuvirtide has been demonstrated in combination with other agents. Its novel mechanism of action offers a low potential for cross-resistance with conventional classes of antiretrovirals, and its extracellular distribution means that drug interactions and intracellular metabolic disturbances are unlikely. Targeting viral fusion or entry will hopefully provide respite for patients who have limited treatment options following the emergence of multi-drug resistance.
Lazzarin
Adriano
A
Vita Salute San Raffaele University, Clinic of Infectious Diseases, via Stamira d'Ancona 20, 20127 Milano, Italy. lazzarin.adriano@hsr.it
D000595:Amino Acid Sequence; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D002986:Clinical Trials as Topic; D004347:Drug Interactions; D024882:Drug Resistance, Viral; D000077560:Enfuvirtide; D015700:HIV Envelope Protein gp41 / Q000009:adverse effects / Q000494:pharmacology*; D023581:HIV Fusion Inhibitors / Q000494:pharmacology*; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*
D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D010446:Peptide Fragments; D000077560:Enfuvirtide