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; ES Daar; A Mills; C Brinson; E DeJesus; FA Post; J Morales-Ramirez; M Thompson; O Osiyemi; B Rashbaum; H-J Stellbrink; C Martorell; H Liu; Y-P Liu; D Porter; SE Collins; D SenGupta; M Das

Disclosures

HIV Medicine. 2018;19(10):724-733. 

In This Article

Abstract and Introduction

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.

Introduction

Regimens in which a nonnucleoside reverse transcriptase inhibitor (NNRTI) is combined with two nucleos(t)ide reverse transcriptase inhibitors (NRTIs) remain among the most commonly prescribed regimens for the treatment of HIV–1 infection worldwide. The NNRTIs efavirenz (EFV) and rilpivirine (RPV) are each coformulated with the NRTIs emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF) as complete single-tablet regimens (STRs): EFV/FTC/TDF and RPV/FTC/TDF, respectively. Where EFV/FTC/TDF was the first once-daily single-tablet regimen, the association of EFV with central nervous system (CNS)–related side effects has curtailed its use as better tolerated options, including RPV, have become available.[1–3] Subsequently, it has been found that regimens containing tenofovir alafenamide (TAF) have improved bone and renal safety compared with TDF-containing regimens, while maintaining excellent efficacy.[4,5]

Rilpivirine/FTC/TAF is a preferred or alternative recommended treatment regimen for initial antiretroviral therapy in European and US treatment guidelines for patients with a CD4 cell count > 200 cells/μL and HIV RNA < 100 000 HIV–1 RNA copies/mL.[6,7] Whether to switch from an effective regimen remains of clinical interest.

We investigated the clinical efficacy, safety and tolerability of switching to RPV/FTC/TAF from a stable regimen of either RPV/FTC/TDF or EFV/FTC/TDF in HIV–1–infected, virally suppressed adults in two distinct but similarly designed randomized controlled trials. The primary 48–week endpoints were previously reported.[5,8] Herein, we present efficacy, safety and tolerability outcomes up to week 96.

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