Abstract Body

Tenofovir alafenamide (TAF) is a novel tenofovir prodrug with reduced risk of bone and renal toxicities compared to tenofovir disoproxil fumarate (TDF). TAF (25 mg) is coformulated with emtricitabine (FTC, 200 mg) and rilpivirine (RPV, 25 mg). The impact of switching to RPV/FTC/TAF single tablet regimen (STR) from other NNRTI-containing STRs RPV/FTC/TDF or efavirenz (EFV)/FTC/TDF was evaluated in two Phase 3 clinical trials. Final efficacy and safety results from Week 96 are presented.

We conducted two randomized, double-blind, active controlled, 96-week, Phase 3 clinical studies in virologically suppressed (HIV-1 RNA <50 c/mL), HIV-1-infected adults with estimated glomerular filtration rate > 50 mL/min, taking either RPV/FTC/TDF (Study 1216) or EFV/FTC/TDF (Study 1160) for at least 6 months. The secondary virologic efficacy (HIV-1 RNA <50 c/mL) endpoint was at Week 96 using the FDA snapshot algorithm with a pre-specified non-inferiority margin of 8%. Bone mineral density (BMD) was measured by DXA and percentage change from baseline compared between treatment groups using ANOVA. Percentage changes from baseline in renal markers were compared between treatment groups using Wilcoxan rank sum test. Adverse events and tolerability were evaluated.

A total of 630 participants were randomized and treated in Study 1216 and 875 in Study 1160. In Studies 1216 and 1160 the median ages were 45 and 49 years, 10% and 13% women, 19% and 27% black respectively. In both studies, switching to RPV/FTC/TAF was non-inferior to continuing baseline therapy through week 96. Study 1216: 89% vs 88% (difference: 0.7%; 95% CI -4.3 to +5.8); Study 1160: 85% vs. 85% (difference 0%; 95% CI -4.8 to +4.8). No participant on RPV/FTC/TAF had treatment emergent resistance versus two on EFV/FTC/TDF and one on RPV/FTC/TDF who was found to have pre-existing NRTI and NNRTI resistance at baseline. Significant increases from baseline in hip and spine BMD and improvements in renal tubular markers were observed in the RPV/FTC/TAF groups compared to continued therapy (p <0.001, Table 1). Fanconi syndrome occurred in one subject on EFV/FTC/TDF, no renal tubulopathy cases occurred on RPV/FTC/TAF.

Switching to RPV/FTC/TAF was safe and maintained high rates of viral suppression through 96 weeks with no cases of treatment emergent resistance. Switching patients to RPV/FTC/TAF is an effective option with improved safety in long-term follow-up.