HIV-1 resistance to reverse transcriptase inhibitors

Abstract

Purpose of Review: This review discusses the mutations and mechanisms associated with HIV-1 resistance to nucleoside reverse transcriptase (RT) inhibitors (NRTIs) and nonnucleoside RT inhibitors (NNRTIs). Recent Findings: First-line antiretroviral therapy (ART) for the treatment of HIV-1 infection typically includes two NRTIs in combination with an NNRTI or a protease inhibitor. NRTIs and NNRTIs are also routinely used in second-line and salvage ART therapies. HIV-1 resistance to all of the FDA-approved NRTIs and NNRTIs has been documented. An understanding of the mutations associated with RT inhibitor (RTI) resistance, the antagonistic or complementary interactions between RTI-resistance mutations, and the mechanisms of HIV-1 resistance to RTIs is of critical importance for the development and formulation of effective ART therapies. Of concern, there has been a significant increase in circulating and transmitted NNRTI drug resistance in resource-limited settings due to the extensive use of NNRTIs in prevention and treatment strategies for HIV-1 infection. Despite this increase in NNRTI drug resistance, the diarylpyrimidine NNRTIs, dapivirine, etravirine, and rilpivirine, will be increasingly used in resourcelimited settings. As such, there is a continued need to monitor and understand NNRTI resistance, particularly in sub-Saharan Africa where non-subtype B HIV-1 predominates. Summary: This review describes HIV-1 resistance to NRTIs and NNRTIs.