Background: The Single-Tablet Regimen (STaR) study (GS-US-264-0110) is a 96-week phase 3b study evaluating the safety and efficacy of 2 single-tablet regimens, rilpivirine/emtricitabine/tenofovir DF (RPV/FTC/TDF), and efavirenz/emtricitabine/tenofovir DF (EFV/FTC/TDF) in treatment-naive HIV-1–infected subjects.
Methods: Genotypic analyses (population sequencing) of HIV-1 protease and reverse transcriptase were performed at screening; subjects with pre-existing resistance to study drugs were excluded. The primary protocol-defined resistance analysis population (RAP) had genotypic/phenotypic analyses at failure and baseline for protease and reverse transcriptase.
Results: At week 48, the primary RAP included 20/394 subjects (5.1%) receiving RPV/FTC/TDF and 7/392 subjects (1.8%) receiving EFV/FTC/TDF. In the RPV/FTC/TDF arm, isolates from 17/394 subjects (4.3%) developed nonnucleoside reverse transcriptase inhibitor (NNRTI) and/or nucleoside reverse transcriptase inhibitor (NRTI) resistance mutations, and 16/17 isolates had both NNRTI and NRTI resistance mutations. In the EFV/FTC/TDF arm, isolates from 3/392 subjects (0.8%) developed NNRTI and/or NRTI resistance mutations. When stratified by baseline viral load of either ≤100,000 or >100,000 copies/mL, 5/260 (1.9%) versus 12/134 (9.0%) RPV/FTC/TDF-treated subjects and 2/250 (0.8%) versus 1/142 (0.7%) EFV/FTC/TDF-treated subjects developed resistant isolates, respectively. The presence of pre-existing NRTI- and NNRTI-associated resistance mutations not excluded at screening (not related to study drugs) did not impact treatment response to either regimen.
Conclusions: Among subjects in the primary RAP, resistance development to RPV/FTC/TDF consisted of NNRTI and NRTI mutations and was more frequent than resistance development to EFV/FTC/TDF. In subjects with baseline viral load ≤100,000 copies/mL, resistance development was low (<2%) for both RPV/FTC/TDF and EFV/FTC/TDF arms and less frequent compared with subjects with baseline viral load >100,000 copies/mL, for RPV/FTC/TDF.