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

PLoS One. 2020 Jan 29;15(1):e0224875. doi: 10.1371/journal.pone.0224875. eCollection 2020.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / administration & dosage
  • Adenine / analogs & derivatives
  • Adult
  • Aged
  • Alanine
  • Benzimidazoles / administration & dosage
  • Coinfection / drug therapy*
  • Coinfection / virology
  • Drug Combinations*
  • Drug Resistance, Viral / drug effects
  • Emtricitabine / administration & dosage
  • Female
  • Fluorenes / administration & dosage
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV-1 / drug effects
  • HIV-1 / pathogenicity
  • Hepacivirus / pathogenicity
  • Hepatitis C / complications
  • Hepatitis C / drug therapy*
  • Hepatitis C / virology
  • Humans
  • Male
  • Middle Aged
  • RNA, Viral / isolation & purification
  • Sofosbuvir / administration & dosage
  • Tenofovir / administration & dosage

Substances

  • Benzimidazoles
  • Drug Combinations
  • Fluorenes
  • RNA, Viral
  • emtricitabine tenofovir alafenamide
  • ledipasvir
  • Tenofovir
  • tenofovir alafenamide
  • Emtricitabine
  • Adenine
  • Alanine
  • Sofosbuvir

Associated data

  • ClinicalTrials.gov/NCT02707601

Grants and funding

The study was funded by Gilead Sciences, Inc., Foster City, CA, USA. The study sponsor, Gilead Sciences, Inc., played a role in the study design, data collection and analysis, decision to publish, and preparation of the manuscript.