Rilpivirine Vs. Efavirenz-Based Single-Tablet Regimens In Treatment-Naive Adults: Week 96 Efficacy And Safety From A Randomized Phase 3b Study

Objectives:To compare efficacy, safety, tolerability, and patient-reported outcomes between two single-tablet regimens, rilpivirine/emtricitabine/tenofovir disoproxil fumarate (RPV/FTC/TDF) and efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF), in HIV-1-infected, treatment-naive adults.Design:This was a phase 3b, 96-week, randomized, open-label, international, noninferiority trial.Methods:A total of 799 participants were randomized (1:1) to receive RPV/FTC/TDF or EFV/FTC/TDF. The primary efficacy endpoint evaluated proportions of participants with HIV-1 RNA less than 50 copies/ml using the Snapshot algorithm. Additional assessments included CD4(+) cell counts, genotypic/phenotypic resistance, adverse events, patient-reported outcomes, and quality of life questionnaires.Results:At week 96, trial completion rates were 80.2% (316/394; RPV/FTC/TDF) and 74.0% (290/392; EFV/FTC/TDF). Overall, RPV/FTC/TDF was noninferior to EFV/FTC/TDF [HIV-1 RNA <50 copies/ml: 77.9 vs. 72.4%, respectively; difference -5.5; 95%CI (-0.6, 11.5); P=0.076]. RPV/FTC/TDF was significantly more efficacious compared with EFV/FTC/TDF in participants with baseline HIV-1 RNA equal to or less than 100000 copies/ml (78.8 vs. 71.2%; P=0.046) and in those with CD4(+) cell count greater than 200cells/l (80.6 vs. 73.0%; P=0.018). There was no significant between-group difference in the CD4(+) cell count increase (278189 vs. 259 +/- 191cells/l; P=0.17). Few participants developed resistance after week 48 (1.0% RPV/FTC/TDF; 0.3% EFV/FTC/TDF). Compared with EFV/FTC/TDF, RPV/FTC/TDF was associated with fewer adverse event-related discontinuations (3.0 vs. 11.0%; P<0.001), significantly fewer adverse events due to central nervous system issues and rash, greater improvements in patient-reported symptoms, and significant improvements in the SF-12v2 quality of life questionnaire mental health composite score (P=0.014).Conclusion:In treatment-naive, HIV-1-infected participants, 96-week RPV/FTC/TDF treatment demonstrated noninferior efficacy and better tolerability than EFV/FTC/TDF. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.