The fusion inhibitor enfuvirtide in recent antiretroviral strategies

Abstract

Dosage adaptations to renal insufficiency are not necessary with enfuvirtide. Spinal fluid concentrations and ombilic cord passage are negligible. Durability of virological responses with enfuvirtide in combinations has been confirmed, in spite of injection-site reactions and twice daily subcutaneous administration. Enfuvirtide should be used with at least one other fully active drug in optimized background therapy in multidrug-experienced populations, a possible exception being with entry inhibitors, which may further benefit from the addition of a third active drug. Data concerning enfuvirtide in antiretroviral combinations show accelerated viral load decline, and the possibility of switching from enfuvirtide to raltegravir without modification of optimized background therapy.

ADS-J1 Inhibits HIV-1 Entry by Interacting with gp120 and Does Not Block Fusion-Active gp41 Core Formation

“…Enfuvirtide (T20, Fuzeon) is a 36-amino-acid synthetic peptide with a sequence identical to a part of the Cterminal heptad repeat 2 (HR2) region of gp41 that binds to the N-terminal heptad repeat 1 (HR1) in an antiparallel manner, forming a coiled-coil structure during the prefusion step. Mutations in the highly conserved amino acid motif 36 to 45 in the HR1 domain confer resistance to T20 (35), providing strong evidence that HR1 is the site of interaction of T20. However, mutations in other regions of HIV-1 envelope (Env) have been also associated with T20 resistance (26,27).…”

HIV-1 Entry Inhibitor Resistance

“…As such, it has a broader antiviral range than coreceptor inhibitors. However, the need for twice-daily subcutaneous injection as a consequence of a short plasma half-life (4 h) has meant that the use of T-20 is limited (Zhang et al 2002;Makinson and Reynes 2009). …”

Use of new antiretroviral drugs and classes in Bahia, Brazil: a real life experience on salvage therapy of AIDS patients

“…Several studies provided strong evidence that even patients with complex drug resistance profile could be successfully treated with a regimen that include new, active ARV drugs. [2][3][4][5][6] or maraviroc (MVC) up to August 2011. After identification of all patients who used or were in use of these ARV drugs, we reviewed the medical records to evaluate clinical characteristics, virological response, and tolerability of ARV regimens containing these new drugs.…”