Switching to coformulated rilpivirine (RPV), emtricitabine (FTC) and tenofovir alafenamide from either RPV, FTC and tenofovir disoproxil fumarate (TDF) or efavirenz, FTC and TDF: 96-week results from two randomized clinical trials

D Hagins, C Orkin, E S Daar, A Mills, C Brinson, E DeJesus, F A Post, J Morales-Ramirez, M Thompson, O Osiyemi, B Rashbaum, H-J Stellbrink, C Martorell, H Liu, Y-P Liu, D Porter, S E Collins, D SenGupta, M Das, D Hagins, C Orkin, E S Daar, A Mills, C Brinson, E DeJesus, F A Post, J Morales-Ramirez, M Thompson, O Osiyemi, B Rashbaum, H-J Stellbrink, C Martorell, H Liu, Y-P Liu, D Porter, S E Collins, D SenGupta, M Das

Abstract

Objectives: The single-tablet regimen rilpivirine, emtricitabine and tenofovir alafenamide (RPV/FTC/TAF) for treatment of HIV-1-infected adults was approved based on bioequivalence. We assessed the clinical efficacy, safety and tolerability of switching to RPV/FTC/TAF from either RPV/FTC/tenofovir disoproxil fumarate (TDF) or efavirenz (EFV)/FTC/TDF.

Methods: We conducted two distinct randomized, double-blind, active-controlled, noninferiority trials in participants taking RPV/FTC/TDF (Study 1216) and EFV/FTC/TDF (Study 1160). Each study randomized virologically suppressed (HIV-1 RNA < 50 copies/mL) adults (1:1) to switch to RPV/FTC/TAF or continue their current regimen for 96 weeks. We evaluated efficacy as the proportion with HIV-1 RNA < 50 copies/mL using the Food and Drug Administration snapshot algorithm and prespecified bone and renal endpoints at week 96.

Results: We randomized and treated 630 participants in Study 1216 (RPV/FTC/TAF, n = 316; RPV/FTC/TDF, n = 314) and 875 in Study 1160 (RPV/FTC/TAF, n = 438; EFV/FTC/TDF, n = 437). In both studies, the efficacy of switching to RPV/FTC/TAF was noninferior to that of continuing baseline therapy at week 96, with respective percentages of patients with HIV RNA < 50 copies/mL being 89.2% versus 88.5% in Study 1216 [difference 0.7%; 95% confidence interval (CI) -4.3 to +5.8%] and 85.2% versus 85.1% in Study 1160 (difference 0%; 95% CI -4.8 to +4.8%). No participant on RPV/FTC/TAF developed treatment-emergent resistance versus two on EFV/FTC/TDF and one on RPV/FTC/TDF. Compared with continuing baseline therapy, significant improvements in bone mineral density and renal tubular markers were observed in the RPV/FTC/TAF groups (P < 0.001).

Conclusions: Switching to RPV/FTC/TAF from RPV/FTC/TDF or EFV/FTC/TDF was safe and effective and improved bone mineral density and renal biomarkers up to 96 weeks with no cases of treatment-emergent resistance.

Keywords: HIV; bone mineral density; renal disease; rilpivirine; tenofovir alafenamide.

© 2018 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.

Figures

Figure 1
Figure 1
Disposition of study participants at week 96. (a) Study 1216: Switch to rilpivirine, emtricitabine and tenofovir alafenamide (RPV/FTC/TAF) from RPV/FTC/tenofovir disoproxil fumarate (TDF). (b) Study 1160: switch to RPV/FTC/TAF from efavirenz (EFV)/FTC/TDF.
Figure 2
Figure 2
Changes in bone mineral density (BMD) at the hip and spine from baseline to week 96. BMD, bone mineral density; CI, confidence interval. P‐values are from the analysis of variance (ANOVA) model including treatment as a fixed effect.

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