No Emergent Resistance in HIV-1 Infected Virologically-Suppressed Subjects Who Switched to R/F/TAF

Abstract

BackgroundGS-US-366-1216 and GS-US-366-1160 are randomized, double-blind, phase 3b studies evaluating the safety and efficacy of switching to rilpivirine/emtricitabine/tenofovir alafenamide (R/F/TAF) from R/F/tenofovir disoproxil fumarate (TDF) or efavirenz (EFV)/F/TDF, respectively, in HIV-1-infected virologically-suppressed subjects. At Week 48, switching to R/F/TAF was non-inferior to staying on R/F/TDF (94% vs. 94%, respectively) or EFV/F/TDF (90% vs. 92%) for HIV-1 RNA <50 c/mL (virologic success) by FDA snapshot analysis. Here, we present integrated resistance analyses of these two studies through Week 48.MethodsHistorical genotypes were collected when available. Subjects in the resistance analysis population (subjects with HIV-1 RNA ≥400 c/mL at virologic failure, discontinuation, or Week 48) had genotypic/phenotypic analyses at failure for protease and reverse transcriptase (RT; PhenoSense GT, Monogram). Subjects with post-baseline resistance mutations detected had their baseline proviral DNA analyzed retrospectively (GenoSure Archive, Monogram).ResultsOf the 1504 randomized and treated subjects, resistance development was analyzed for 7 subjects (0.9%; 7/754) on R/F/TAF, 1 subject (0.3%; 1/313) on R/F/TDF, and 2 subjects (0.5%; 2/437) on EFV/F/TDF. No R/F/TAF (0%) or R/F/TDF (0%) subjects developed primary NNRTI or NRTI resistance mutations. One EFV/F/TDF subject (0.2%; 1/437) developed primary NNRTI and NRTI resistance mutations (NNRTI: Y188L; NRTI: M184V). Three subjects on R/F/TAF had virologic rebound with mutations also detected at baseline by proviral DNA analysis. Historical genotypes were available for 527 subjects; virologic success rates were high among subjects with pre-existing mutations (Table 1).Table 1.Virologic success rates of subjects with mutations by historical genotype.RT mutationSubjects with success/subjects with mutation (%)R/F/TAFR/F/TDFEFV/F/TDFK101E1/1 (100%)00K103N10/11a (91%)6/7a (86%)1/1 (100%)E138A/K2/3a (67%)2/2 (100%)0M184V1/2a (50%)1/1 (100%)0 a1 subject discontinued prior to Week 48 with HIV-1 RNA <50 c/mL.ConclusionNo emergent resistance to any of the components of R/F/TAF was detected through 48 weeks after switching. Virologic success rates were high among subjects with pre-existing mutations.Disclosures D. Porter, Gilead Sciences, Inc.: Employee and Shareholder, Salary; R. Kulkarni, Gilead Sciences, Inc.: Employee and Shareholder, Salary; H. Cao, Gilead Sciences, Inc.: Employee and Shareholder, Salary; D. Sengupta, Gilead Sciences Inc.: Employee and Shareholder, Salary; K. White, Gilead Sciences, Inc.: Employee and Shareholder, Salary