STAR Study: single tablet regimen emtricitabine/rilpivirine/tenofovir DF is non‐inferior to efavirenz/emtricitabine/tenofovir DF in ART‐naïve adults

Abstract

Simplified antiretroviral treatment (ART) regimens improve quality of life and long‐term medication adherence. Emtricitabine/rilpivirine/tenofovir DF (FTC/RPV/TDF) is a well‐tolerated, once daily single tablet regimen (STR) treatment option. This is the first study to directly compare the safety and efficacy of the two STRs FTC/RPV/TDF and efavirenz/emtricitabine/tenofovir DF (EFV/FTC/TDF) in treatment‐naïve adults. STaR is a randomized, open‐label, multi‐center, international, 96‐week study to evaluate the safety and efficacy of the STR FTC/RPV/TDF compared to the STR EFV/FTC/TDF in treatment‐naïve HIV‐1‐infected subjects. Subjects were randomized 1:1 to FTC/RPV/TDF or EFV/FTC/TDF. Eligibility criteria included screening HIV‐1 RNA ≥2,500 c/mL, genotypic sensitivity to EFV, FTC, TDF, and RPV, and no prior ARV therapy. Randomization was stratified by HIV‐1 RNA level (≤100,000 c/mL or >100,000 c/mL) at screening. The primary endpoint was the proportion of subjects with HIV‐1 RNA <50 c/mL at Week 48 as determined by the FDA snapshot algorithm (12% pre‐specified non‐inferiority margin). A total of 784 subjects were randomized and received at least one dose of study drug (392 FTC/RPV/TDF; 392 EFV/FTC/TDF). Baseline characteristics were similar in both treatment arms, with a baseline mean CD4 count of 390 cells/mm 3 . and HIV‐1 RNA of 4.8 log 10 c/mL. FTC/RPV/TDF was non‐inferior to EFV/FTC/TDF (86% vs 81%) at Week 48 for HIV RNA <50 c/mL (difference 4.0%, 95% CI [‐1.2%, 9.2%]) per FDA snapshot analysis. Superior efficacy was demonstrated for baseline HIV‐1 RNA ≤100,000 c/mL (n=508), 88% FTC/RPV/TDF vs 81% EFV/FTC/TDF (difference 7.2%, 95% CI [0.9%, 13.4%]), and non‐inferior for >100,000 c/mL (n=276), 80% FTC/RPV/TDF vs 82% EFV/FTC/TDF (difference −1.8%, 95% CI [−11.2%, 7.5%]). Overall, virologic failure, defined as HIV RNA ≥50 c/mL at Week 48, discontinuation due to lack of efficacy per investigator or discontinuation of study drug for reasons other than an adverse event (AE) with HIV RNA ≥50 copies/mL was 8% for FTC/RPV/TDF vs 6% for EFV/FTC/TDF (difference 2.7%, 95% CI [−0.9%, 6.3%]). There were fewer study drug discontinuations due to AEs in the FDA snapshot analysis in FTC/RPV/TDF (2%) compared to EFV/FTC/TDF (8%). The STR FTC/RPV/TDF demonstrated overall non‐inferior efficacy and improved tolerability compared to the STR EFV/FTC/TDF as well as superior efficacy for subjects with a baseline viral load ≤100,000 c/mL in treatment‐naïve HIV‐1‐infected subjects.