Journal
FUTURE MICROBIOLOGY
Volume 10, Issue 11, Pages 1773-1782Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/fmb.15.106
Keywords
HIV; mutations; nucleoside; non-nucleoside; resistance; reverse transcriptase
Categories
Funding
- NIH, USA [AI081571, GM068406, AI071846]
- NIH CFAR [2P30-AI-050409]
- Department of Veterans Affairs
- Canadian Institutes for Health Research
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [P30AI050409, R01AI071846, R01AI081571] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM068406] Funding Source: NIH RePORTER
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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.
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