Transmitted drug-resistant HIV type 1 remains prevalent and impacts virologic outcomes despite genotype-guided antiretroviral therapy

Trends in transmitted drug resistance-associated mutations (TDRM) in HIV-1infection vary depending on geographic and cohort characteristics. The impact of TDRM among patients receiving fully active combination antiretroviral therapy (cART) is poorly characterized. This was a retrospective study of 801 HIV-1-infected treatment-naive patients from 2001 to 2009 who had pre-cART genotype resistance test results available. The prevalence of TDRM was compared for each year strata. Multivariate Cox proportional hazards regression models were used to assess factors associated with virologic failure at 48 weeks. TDRM was detected in 136 (17%) patients with ≥2 class TDRM in 20 patients. K103N/S was the most frequent (n=77). There were no changes in the prevalence of mutations over time (P _trend=0.67). Six hundred and eleven patients were started on cART. Virologic failure occurred in 38% of those with TDRM and 24% of those without (p<0.01). In multivariate analysis, nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance was associated with a 1.5-fold increased risk of virologic failure. TDRM remains common among treatment-naive HIV-1-infected patients, affecting one in six patients. Transmission of NNRTI drug resistance was associated with risk of virologic failure despite initiation of genotype-guided cART.