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Review
. 2014 Jul 31;6(8):2960-73.
doi: 10.3390/v6082960.

The emerging profile of cross-resistance among the nonnucleoside HIV-1 reverse transcriptase inhibitors

Nicolas Sluis-Cremer  1
Affiliations
Review

The emerging profile of cross-resistance among the nonnucleoside HIV-1 reverse transcriptase inhibitors

Nicolas Sluis-Cremer. Viruses. .

Abstract

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are widely used to treat HIV-1-infected individuals; indeed most first-line antiretroviral therapies typically include one NNRTI in combination with two nucleoside analogs. In 2008, the next-generation NNRTI etravirine was approved for the treatment of HIV-infected antiretroviral therapy-experienced individuals, including those with prior NNRTI exposure. NNRTIs are also increasingly being included in strategies to prevent HIV-1 infection. For example: (1) nevirapine is used to prevent mother-to-child transmission; (2) the ASPIRE (MTN 020) study will test whether a vaginal ring containing dapivirine can prevent HIV-1 infection in women; (3) a microbicide gel formulation containing the urea-PETT derivative MIV-150 is in a phase I study to evaluate safety, pharmacokinetics, pharmacodynamics and acceptability; and (4) a long acting rilpivirine formulation is under-development for pre-exposure prophylaxis. Given their widespread use, particularly in resource-limited settings, as well as their low genetic barriers to resistance, there are concerns about overlapping resistance between the different NNRTIs. Consequently, a better understanding of the resistance and cross-resistance profiles among the NNRTI class is important for predicting response to treatment, and surveillance of transmitted drug-resistance.

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Figures

Figure 1
Figure 1
Chemical structures of nonnucleoside reverse transcriptase inhibitors (NNRTIs) used in HIV-1 prevention and treatment strategies.
Figure 2
Figure 2
Expanding use of NNRTIs in HIV-1 prevention and treatment strategies.
See this image and copyright information in PMC

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