The-incidence of HIV drug resistance and its impact on progression of HIV disease among antiretroviral-naive participants started on three different antiretroviral therapy strategies

Treatment-naive participants were randomized to three antiretroviral strategies (all with nucleoside reverse transcriptase inhibitor [NRTI] background): protease inhibitor (PI), non-nucleoside reverse transcriptase inhibitor (NNRTI), or PI+NNRTI. The strategies were compared for drug resistance at first virologic failure (VF; HIV RNA > 1000 copies/mL). The impact of resistance on AIDS or death was determined. Method: Drug resistance was determined by genotype. Cox models were used to compare the strategies for VF with resistance and to determine the impact of resistance on AIDS or death. Results: Of 1,360 participants, 866 experienced VF; 226 experienced AIDS or death (median follow-up 5 years). Rates (per 100 person-years) for VF with resistance were 14.9 (PI), 10.8 (NNRTI), and 11.5 (PI+NNRTI); hazard ratio (HR) was 0.78 (950A Cl 0.61-0.99) for NNRTI versus Pl. Compared to those with no VF, there was a significantly increased risk of AIDS or death for participants with solitary NNRT1 resistance (HR 2.31, 95% CI 1.46-3.66) and for those failing with no known resistance (HR 1.78, 95% CI 1.18-2.68). Participants failing with solitary NNRTI resistance and with no resistance had the lowest percent of time on antiretroviral treatment (ART) and the lowest cumulative mean adherence scores. Conclusion: For treatryient-ndNe participants, the risk of AIDS or death is increased for those who failed virologically with solitary NNRTI resistance and those who failed with no known drug resistance compared to those with no virologic failure. Both the lack of ART exposure in nonadherent participants and the development of NNRTI resistance among those who take and fail their ART regimen predict poor clinical outcomes.