These data demonstrate durable efficacy of enfuvirtide plus OB over 48 weeks.

The end of the twentieth century saw dramatic improvements in the prognosis of HIV infection brought about by the introduction of new agents (the protease inhibitors and the non-nucleoside reverse transcriptase inhibitors) and their use in highly active combinations. However, the durability of these combination treatments is limited by a number of factors including adverse effects and extensive intra-class cross-resistance so that new antiretrovirals acting on alternative targets and having improved systemic tolerability profiles are required. The HIV binding and entry process offers several potential targets for antiviral interaction. These include gp120 binding to CD4 and to chemokine co-receptor molecules as well as the fusion process itself, which involves interactions between two leucine zipper-like 4-3 repeat regions within gp41 known as heptad repeat (HR)1 and HR2. Peptides such as enfuvirtide (formerly DP178 or T-20), that mimic the HR2 region of gp41, inhibit HIV-1 by a mechanism that is thought to involve competitive binding to HR1. This review summarises the clinical development of enfuvirtide, providing an overview of the pharmacokinetic, efficacy and safety data in various patient populations, and also considers the evidence for the key role of genotypic changes in the HR1 region (amino acids 36-45) in determining viral susceptibility to inhibition by enfuvirtide.

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The addition of enfuvirtide to an optimized background regimen does not exacerbate AEs commonly associated with antiretrovirals. ISRs limited treatment in <5% of patients.

Antiretroviral therapy effectively suppressed HIV-1 replication in GALT. The percentage of CD4+ T cells in peripheral blood uniformly increased in all study subjects, whereas it was more variable in the GALT.