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Viruses 2014, 6(8), 2960-2973; https://doi.org/10.3390/v6082960

The Emerging Profile of Cross-Resistance among the Nonnucleoside HIV-1 Reverse Transcriptase Inhibitors

Department of Medicine, Division of Infectious Diseases, University of Pittsburgh School of Medicine, S817 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, USA
Received: 2 June 2014 / Revised: 17 July 2014 / Accepted: 22 July 2014 / Published: 31 July 2014
(This article belongs to the Special Issue HIV Drug Resistance)
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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. View Full-Text
Keywords: HIV; reverse transcriptase; nonnucleoside inhibitors; nevirapine; efavirenz; rilpivirine; etravirine; dapivirine; MIV-150 HIV; reverse transcriptase; nonnucleoside inhibitors; nevirapine; efavirenz; rilpivirine; etravirine; dapivirine; MIV-150
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Sluis-Cremer, N. The Emerging Profile of Cross-Resistance among the Nonnucleoside HIV-1 Reverse Transcriptase Inhibitors. Viruses 2014, 6, 2960-2973.

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