Mutations in HIV-1 reverse transcriptase potentially associated with hypersusceptibility to nonnucleoside reverse-transcriptase inhibitors: Effect on response to efavirenz-based therapy in an urban observational cohort

Background. Hypersusceptibility to nonnucleoside reverse-transcriptase inhibitors (NNRTIs) was described in association with reverse-transcriptase (RT) mutations conferring resistance to nucleoside reverse-transcriptase inhibitors (NRTIs). We evaluated the effect of RT mutations associated with hypersusceptibility to NNRTIs on the response to efavirenz-based therapy. Methods. We analyzed an observational database of patients for whom highly active antiretroviral therapy failed and who received genotypic resistance testing-guided therapy, either efavirenz or protease inhibitor (PI) based. Study end points were achievement of virus load 500 copies/mL, and changes in CD4 cell counts. Results. The baseline RT mutations M41L, M184V, L210W, and T215Y and the M41L/T215Y and M41L/ T215Y/M184V combinations were associated with virological suppression for efavirenz-treated patients, whereas, for PI-treated patients, only the M184V mutation was associated with virological suppression, and the L210W mutation showed a negative correlation; no correlation was found between any mutation and virological response without rebound. Conclusions. The M41L, M184V, L210W, and T215Y mutations were associated with a better, although transient, virological outcome in patients treated with efavirenz-based regimens.