Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations

Objectives:We characterized pairwise and higher order patterns of non-nucleoside reverse transcriptase inhibi-tor (NNRTI)-selected mutations because multiple mutations are usually required for clinically significant resist-ance to second-generation NNRTIs. Patients and methods: We analysed viruses from 13039 individuals with sequences containing at least one of 52 published NNRTI-selected mutations, including 1133 viruses from individuals who received efavirenz but no other NNRTI and 1510 viruses from individuals who received nevirapine but no other NNRTI. Of the 17 reported etravirine resistance-associated mutations (RAMs), Y181C/I/V, L100I, K101P and M230L were considered major based on published in vitro susceptibility data