Adherence and Preexisting Major Protease Inhibitor Resistance Mutations are Associated with Virologic Failure of a Dual-Class Antiretroviral Regimen with Inhibitors of HIV-1 Viral Protease and Integrase

OBJECTIVES: Novel treatment strategies are needed for treatment-experienced HIV-infected individuals. We retrospectively evaluated virologic outcomes on a dual-class, protease inhibitor (PI) plus raltegravir, antiretroviral (ARV) regimen. METHODS: Virologic success was defined by a plasma HIV-RNA level ≤200 copies/mL. Adherence was measured using pharmacy refill data. The association between adherence and virologic failure was assessed using bivariate logistic regression. RESULTS: In 39 individuals, median prior antiretroviral therapy (ART) exposure was 11 years. Of 39 individuals, 36 (92%) achieved an HIV-RNA ≤200 copies/mL. After a median follow-up of 328 days (interquartile range [IQR] 190-737 days), 74% maintained an HIV-RNA <200 copies/mL but only 44% had <50 copies/mL. Median adherence was 96.4% (IQR 83.3%-100%). For every 10% decrease in adherence, the odds of virologic failure increased by 90% (odds ratio [OR] = 1.9, 95% confidence interval [CI] 1.1-3.3). In all, 4 individuals had ≥2 preexisting major PI resistance mutations and all 4 had virologic failure. CONCLUSIONS: Most treatment-experienced individuals achieved virologic suppression on a dual-class regimen of a PI plus raltegravir. Success was limited by poor medication adherence and preexisting major PI resistance mutations.