Efficacy and safety of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide in Asian participants with human immunodeficiency virus 1 infection: A sub-analysis of phase 3 clinical trials

Abstract

Background: The efficacy and safety of a single tablet regimen (STR) of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) was analyzed in Phase 3 clinical trials in antiretroviral therapy (ART)-naive and ART-experienced Asian participants infected with human immunodeficiency virus (HIV)-1 through 96 or 144 weeks.

Objective: In Asian population requiring treatment, it is imperative to have data specific to this group, particularly as there is a general concern that Asians with lower body weight have increased risk of tenofovir disoproxil fumarate (TDF)-related renal dysfunction.

Methods: Studies -104 and 111 were randomized, double-blind, placebo-controlled, 144-week studies conducted in ART-naive participants, comparing E/C/F/TAF versus E/C/F/TDF. Study 109 was a randomized, open-label, 96-week study conducted in virologically suppressed, ART-experienced participants, who switched to E/C/F/TAF from ritonavir/cobicistat-boosted atazanavir ATV+(RTV or COBI) + F/TDF regimens, from non-nucleoside reverse transcriptase inhibitors (NNRTI) + F/TDF regimens, or from E/C/F/TDF. Study 112 was a single arm, open-label, 144-week study conducted in HIV suppressed, ART-experienced participants with mild-moderate renal impairment, who switched to E/C/F/TAF.

Results: Asian participants in these studies had sustained efficacy safety and tolerability. In Study 104/111, Asian participants achieved 93% virologic suppression on TAF vs 88% on TDF at week 144. At baseline, there were numerically more Asians with median CD4 counts < 200 cells/uL and VL > 100,000 c/mL. In Study 109, 95% of Asians on TAF vs 86% on TDF maintained virologic suppression at week 96. Lastly, in Study 112, 91% maintained virologic suppression at week 144. There were no discontinuations due to renal AE, no cases of PRT or Fanconi syndrome in any of the studies.

Keywords:

• HIV-1
• Genvoya
• Stribild
• Asian subanalysis
• HIV renal impairment
• Tx-naïve
• Tx-experienced
• elvitegravir
• TAF
• TDF
• tenofovir

Acknowledgments

The authors would like to acknowledge and thank the patients who participated in these studies, as well as the site and study management staff whose effort made this study possible. All investigators and sites that participated in these studies have previously published their respective results.

Notes on contributors

Yeon-Sook Kim, MD practices at Chungnam National University, Daejeon, South Korea. Primary investigator for elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide.

Shinichi Oka, MD practices at National Center for Global Health and Medicine Hospital, Tokyo, Japan. Primary investigator for elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide. Not receiving funding from Gilead Sciences.

Ploenchan Chetchotisakd, MD practices at Khon Kaen University, Khon Kaen, Thailand. Primary investigator for elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide. Not receiving funding from Gilead Sciences.

Amanda Clarke, MD practices at Brighton and Sussex University Hospitals NHS Trust, Brighton, UK. Primary investigator for elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide. Not receiving funding from Gilead Sciences.

Khuanchai Supparatpinyo, MD practices at Chiang Mai University, Chiang Mai, Thailand. Primary investigator for elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide. Not receiving funding from Gilead Sciences.

Anchalee Avihingsanon, MD practices at Thai Red Cross AIDS Research Centre, Bangkok, Thailand. Primary investigator for elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide. Not receiving funding from Gilead Sciences.

Winai Ratanasuwan, MD practices at Siriraj Hospital, Mahidol University, Bangkok, Thailand. Primary investigator for elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide. Not receiving funding from Gilead Sciences.

Sasisopin Kiertiburanakul, MD practices at Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. Primary investigator for elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide. Not receiving funding from Gilead Sciences.

Kiat Ruxrungtham, MD practices at Thai Red Cross AIDS Research Centre (HIV-NAT). Primary investigator for elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide. Not receiving funding from Gilead Sciences.

Do Tran, SangYoun Yang, Susan Guo, YaPei Liu, Moupali Das, Damian McColl, Roberto Corales, Chris Nguyen are employee at Gilead Sciences.