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Review
. 2015;10(11):1773-82.
doi: 10.2217/fmb.15.106. Epub 2015 Oct 30.

Resistance to reverse transcriptase inhibitors used in the treatment and prevention of HIV-1 infection

Nicolas Sluis-Cremer  1 , Mark A Wainberg  2 , Raymond F Schinazi  3   4
Affiliations
Review

Resistance to reverse transcriptase inhibitors used in the treatment and prevention of HIV-1 infection

Nicolas Sluis-Cremer et al. Future Microbiol. 2015.

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.

Keywords: HIV; mutations; non-nucleoside; nucleoside; resistance; reverse transcriptase.

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Figures

Figure 1
Figure 1
Structures of RTIs approved for clinical use
Figure 2
Figure 2
Structures of RTIs in clinical development
See this image and copyright information in PMC

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