HIV/HCV therapy with ledipasvir/sofosbuvir after randomized switch to emtricitabinetenofovir alafenamide-based single-tablet regimens

Gregory D. Huhn, Moti Ramgopal, Mamta K. Jain, Federico Hinestrosa, David M. Asmuth, Jihad Slim, Deborah Goldstein, Shauna Applin, Julie H. Ryu, Shuping Jiang, Stephanie Cox, Moupali Das, Thai Nguyen-Cleary, David Piontkowsky, Bill Guyer, Lorenzo Rossaro, Richard H. Haubrich

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction Guidelines advocate the treatment of HCV in all HIV/HCV co-infected individuals. The aim of this randomized, open-label study (ClinicalTrials.gov identifier: NCT02707601; https:// clinicaltrials.gov/ct2/show/NCT02707601) was to evaluate the safety/efficacy of ledipasvir/ sofosbuvir (LDV/SOF) co-administered with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) or rilpivirine/F/TAF (R/F/TAF) in HIV-1/HCV co-infected participants. Methods Participants with HIV-1 RNA <50 copies/mL and chronic HCV-genotype (GT) 1 (HCV treatment- naïve ± compensated cirrhosis or HCV treatment-experienced non-cirrhotic) were randomized 1:1 to switch to E/C/F/TAF or R/F/TAF. If HIV suppression was maintained at Week 8, participants received 12 weeks of LDV/SOF. The primary endpoint was sustained HCV virologic response 12 weeks after LDV/SOF completion (SVR12). Results Of 150 participants, 148 received ≥1 dose of HIV study drug and 144 received LDV/SOF (72 in each F/TAF group; 83% GT1a, 94% HCV treatment-naïve, 12% cirrhotic). Overall, SVR12 was 97% (95% confidence interval: 93-99%). Black race did not affect SVR12. Of four participants not achieving SVR12, one had HCV relapse, one had HCV virologic non- response due to non-adherence, and two missed the post-HCV Week 12 visit. Of 148 participants, 96% receiving E/C/F/TAF and 95% receiving R/F/TAF maintained HIV suppression at Week 24; no HIV resistance was detected. No participant discontinued LDV/SOF or E/C/ F/TAF due to adverse events; one participant discontinued R/F/TAF due to worsening of pre-existing hypercholesterolemia. Renal toxicity was not observed in either F/TAF regimen during LDV/SOF co-administration. In conclusion, high rates of HCV SVR12 and maintenance of HIV suppression were achieved with LDV/SOF and F/TAF-based regimens. Conclusion This study supports LDV/SOF co-administered with an F/TAF-based regimen in HIV-1/ HCV-GT1 co-infected patients.

Original languageEnglish (US)
Article numbere0224875
JournalPloS one
Volume15
Issue number1
DOIs
StatePublished - Jan 1 2020

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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