Resistance to reverse transcriptase inhibitors used in the treatment and prevention of HIV-1 infection. (November 2015)

• Record Type: Journal Article
• Authors: Sluis-Cremer, Nicolas; Wainberg, Mark A; Schinazi, Raymond F
• Is Part Of: Future microbiology. Volume 10:Number 11(2015:Nov.)
• Page Start: 1773
• Page End: 1782
• Publication Date: 2015-11
• Subjects: HIV -- mutations -- nucleoside -- non-nucleoside -- resistance -- reverse transcriptase; Microbiology -- Research -- Periodicals; 616.9041
• DOI: 10.2217/fmb.15.106
• Languages: English
• ISSNs: 1746-0913

Abstract

Inhibitors that target the retroviral enzyme reverse transcriptase (RT) have played an indispensable role in the treatment and prevention of HIV-1 infection. They can be grouped into two distinct therapeutic groups, namely the nucleoside and nucleotide RT inhibitors (NRTIs), and the non-nucleoside RT inhibitors (NNRTIs). NRTIs form the backbones of most first- and second-line antiretroviral therapy (ART) regimens formulated for the treatment of HIV-1 infection. They are also used to prevent mother-to-child transmission, and as pre-exposure prophylaxis in individuals at risk of HIV-1 infection. The NNRTIs nevirapine (NVP), efavirenz and rilpivirine also used to form part of first-line ART regimens, although this is no longer recommended, while etravirine can be used in salvage ART regimens. A single-dose of NVP administered to both mother and child has routinely been used in resource-limited settings to reduce the rate of HIV-1 transmission. Unfortunately, the development of HIV-1 resistance to RT inhibitors can compromise the efficacy of these antiviral drugs in both the treatment and prevention arenas. Here, we provide an up-to-date review on drug-resistance mutations in HIV-1 RT, and discuss their cross-resistance profiles, molecular mechanisms and clinical significance.