Abstract
In the mid 1990s, the introduction of protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (RTIs) enabled combinations of antiretroviral agents to be used in therapeutic regimens to treat HIV-infected patients. Such combination therapy often resulted in potent suppression of viral RNA and was generally accompanied by dramatically improved clinical outcomes for patients with HIV infection [1]. The potent suppression of HIV RNA led to such combinations of antiretroviral agents being referred to as highly active antiretroviral therapy (HAART), and this approach to treatment of HIV disease has resulted in striking and sustained decreases in AIDS-related death since its introduction in 1996 [2]. Prior to the 2003 approval and introduction of Enfuvirtide (FuzeonTM, formerly known as T-20), the first fusion inhibitor, only three classes of antiretrovirals were available for the treatment of HIV: the RTIs - either nucleoside or non-nucleoside - and PIs. Although combinations of these agents brought about dramatic improvements in HIV therapy, the limitations of therapeutic regimens based solely on RTIs and PIs were already evident and problematic when enfuvirtide entered clinical development. These limitations included adverse effects associated with treatment [3, 4], significant drug-drug interactions [5] and the selection of drug-resistant viruses with extensive intra-class cross-resistance [6]. Consequently, an unmet medical need existed (and still remains) for new classes of antiretroviral agents with both improved safety and tolerability profiles, and which circumvent the problems associated with intra-class cross-resistance by acting on alternative targets to inhibit viral replication.
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Greenberg, M.L. (2007). Enfuvirtide: from basic science to FDA approval. In: Reeves, J.D., Derdeyn, C.A. (eds) Entry Inhibitors in HIV Therapy. Milestones in Drug Therapy. Birkhäuser Basel. https://doi.org/10.1007/978-3-7643-7783-0_11
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