Resistance to Non-Nucleoside Reverse Transcriptase Inhibitors

Abstract

The prevalence of non-nucleoside reverse transcriptase (RT) inhibitor (NNRTI) resistance is increasing, especially as the number of patients who have been treated with this class of agents has grown. The three Food and Drug Administration-approved NNRTIs, efavirenz, nevirapine, and delaviridine, have been shown to be potent additions to the antiretroviral (ARV) armamentarium. In many studies, these compounds have been shown to be effective components of highly active ARV therapeutic (HAART) regimens; results have been similar to or better than the comparator protease inhibitors (PIs). Resistance to the NNRTIs occurs more frequently than resistance to other classes of ARVs and is a serious limitation to their use. The use of these agents in monotherapy and in partially suppressive regimens rapidly selects for resistance, and this resistance precludes the use of the other agents in this class. When considering these agents in newly infected or ARV-naive patients, the rate of transmitted resistance, especially in areas in which NNRTIs have been used extensively, may ultimately limit the usefulness of this class of therapeutics. As the incidence of transmission of NNRTI resistance increases, resistance testing for recently infected patients should be strongly considered. The potency of these agents must be balanced against the rapid development of resistance.