Looking for an Active Conformation of the Future HIV Type-1 Non-Nucleoside Reverse Transcriptase Inhibitors

Citations Over Time

Abstract

HIV type-1 (HIV-1) non-nucleoside reverse transcriptase inhibitors (NNRTIs) are key drugs of highly active antiretroviral therapy (HAART) in the clinical management of AIDS/HIV infection. NNRTI-based HAART regimes effectively suppress viral reproduction, are not cytotoxic and show favourable pharmacokinetic properties. First-generation NNRTIs suffer the rapid selection of viral variants, hampering the binding of inhibitors into the reverse transcriptase (RT) non-nucleoside binding site (NNBS). Efforts to improve these first inhibitors led to the discovery of second-generation NNRTIs that proved to be effective against the drug-resistant mutant HIV-1 strains. The success of such agents launched a new season of NNRTI design and synthesis. This paper reviews the characteristics of second-generation NNRTIs, including etravirine, rilpivirine, RDEA-806, UK-453061, BIRL 355 BS, IDX 899, MK-4965 and HBY 097. In particular, the binding modes of these inhibitors into the NNBS of the HIV-1 RT and the most clinically relevant mutant RTs are analysed and discussed.

Related Papers

• → Effect of Mutations at Position E138 in HIV-1 Reverse Transcriptase and Their Interactions with the M184I Mutation on Defining Patterns of Resistance to Nonnucleoside Reverse Transcriptase Inhibitors Rilpivirine and Etravirine(2013)71 cited
• → Looking for an Active Conformation of the Future HIV Type-1 Non-Nucleoside Reverse Transcriptase Inhibitors(2010)60 cited
• → Etravirine and Rilpivirine: Nonnucleoside Reverse Transcriptase Inhibitors with Activity Against Human Immunodeficiency Virus Type 1 Strains Resistant to Previous Nonnucleoside Agents(2009)43 cited
• → Occurrence of etravirine/rilpivirine-specific resistance mutations selected by efavirenz and nevirapine in Kenyan patients with non-B HIV-1 subtypes failing antiretroviral therapy(2014)10 cited
• → Etravirine: Clinical review of a treatment option for HIV type-1-infected patients with non-nucleoside reverse transcriptase inhibitor resistance(2010)8 cited