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

doi:10.1111/hiv.12664

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

HIV Med. 2018 Nov;19(10):724-733. doi: 10.1111/hiv.12664. Epub 2018 Aug 12.

Authors

D Hagins¹, C Orkin², E S Daar³, A Mills⁴, C Brinson⁵, E DeJesus⁶, F A Post⁷, J Morales-Ramirez⁸, M Thompson⁹, O Osiyemi¹⁰, B Rashbaum¹¹, H-J Stellbrink¹², C Martorell¹³, H Liu¹⁴, Y-P Liu¹⁴, D Porter¹⁴, S E Collins¹⁴, D SenGupta¹⁴, M Das¹⁴

Affiliations

¹ Georgia Department of Public Health, Chatham Care Center, Savannah, GA, USA.
² Grahame Hayton Unit, Royal London Hospital and Queen Mary University, London, UK.
³ Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
⁴ Mills Clinical Research, Los Angeles, CA, USA.
⁵ Central Texas Clinical Research, Austin, TX, USA.
⁶ Orlando Immunology Center, Orlando, FL, USA.
⁷ King's College Hospital, London, UK.
⁸ Clinical Research Puerto Rico Inc., San Juan, Puerto Rico.
⁹ AIDS Research Consortium of Atlanta, Atlanta, GA, USA.
¹⁰ Triple O Research Institute PA, West Palm Beach, FL, USA.
¹¹ Capital Medical Associates, Washington, DC, USA.
¹² ICH Study Center, Hamburg, Germany.
¹³ The Research Institute, Springfield, MA, USA.
¹⁴ Gilead Sciences Inc, Foster City, CA, USA.

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.

Publication types

Clinical Trial
Randomized Controlled Trial

MeSH terms

Adult
Anti-Retroviral Agents / administration & dosage*
Anti-Retroviral Agents / adverse effects
Antiretroviral Therapy, Highly Active / adverse effects
Antiretroviral Therapy, Highly Active / methods*
Double-Blind Method
Drug Combinations*
Drug Substitution / adverse effects
Drug Substitution / methods*
Female
HIV Infections / drug therapy*
HIV-1 / isolation & purification
Humans
Male
Middle Aged
RNA, Viral / blood
Treatment Outcome
Viral Load

Substances

Anti-Retroviral Agents
Drug Combinations
RNA, Viral