Prevalence and risk factors for etravirine resistance among patients failing on non-nucleoside reverse transcriptase inhibitors

Background: Prevalence and factors associated with etravirine (ETV) resistance mutations among patients failing on first-generation non-nucleoside reverse transcriptase inhibitors (NNRTI) merit investigation. Methods: The study comprised an analysis of all sequential patients attending the Institute of Infectious Diseases (Brescia, northern Italy) who performed a genotypic resistance testing (GRT) after >= 3 months of a stable NNRTI-based regimen between 2001 and 2006. Multivariable ordinal logistic regression analysis was performed to assess predictors of ETV resistance mutations. Results: Out of 248 strains, 153 (61.7%) harboured >= 1 ETV resistance mutations. In particular, 88 (35.5%), 53 (21.4%) and 12 (4.8%) harboured one, two and three mutations, respectively. The most frequent mutations were G190A (23%), Y181C (23%) and K101E (14.1%). Use of nevirapine (odds ratio [OR] 2.73; 95% confidence level [CI] 1.62-4.62; P<0.001) and a longer time frame between first HIV RNA >500 copies/ml and GIRT (per month, OR 1.05; 95% CI 1.01 -1.09; P=0.01 2) were associated with a greater number of ETV resistance mutations. Conversely, higher CID4(+) T-cell counts at nadir (per 100 cells/mm(3), OR 0.81; 95% CI 0.67-0.98; P=0.029) and use of lamivudine/emtricitabine (OR 0.57; 95% CI 0.37-0.87; P=0.009) were protective. Accumulation of ETV resistance-associated mutations was demonstrated by sequential GRT in 4/35 patients (all treated with nevirapine). Conclusions: Mutations associated with ETV resistance were common among patients failing on NNRTI, but prevalence of viral strains harbouring three mutations was low. Use of efavirenz and co-administration of lamivudine reduced the risk of ETV resistance. The continued use of the current NNRTI in a failing regimen may select for additional resistant variants.