Evaluation of Safety and Effectiveness of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Switch Followed by Ledipasvir/Sofosbuvir HCV Therapy in HIV-HCV Coinfection

Mary-Anne Doyle; Terry Lee; Joel Singer; Angela Crawley; Marina Klein; Curtis Cooper

doi:10.1093/ofid/ofz318

Evaluation of Safety and Effectiveness of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Switch Followed by Ledipasvir/Sofosbuvir HCV Therapy in HIV-HCV Coinfection

Open Forum Infect Dis. 2019 Jul 1;6(7):ofz318. doi: 10.1093/ofid/ofz318.

Authors

Mary-Anne Doyle^{1

2}, Terry Lee³, Joel Singer³, Angela Crawley², Marina Klein^{3

4}, Curtis Cooper^{2

3

5}

Affiliations

¹ Division of Endocrinology and Metabolism, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
² Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
³ CIHR Canadian HIV Trials Network, School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada.
⁴ Department of Medicine, McGill University, Montreal, Quebec, Canada.
⁵ Division of Infectious Diseases, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.

Abstract

Background: We conducted a pilot study assessing the feasibility, efficacy, and safety of a simplified combination HIV antiretroviral and hepatitis C virus (HCV) antiviral regimen in HIV-HCV coinfection.

Methods: Participants on suppressive antiretrovirals and HCV genotype 1 infection were switched to single-tablet daily-dosed elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) and 1 month later initiated single-tablet-regimen daily-dosed ledipasvir-sofosbuvir for 12 weeks. E/C/F/TAF was continued during HCV treatment and for 12 weeks after.

Results: Twenty-six individuals were screened, 25 enrolled, and 23 completed all HIV and HCV treatment. Participants were predominantly male, with a mean age (SD) of 55 (7.5) years. The median transient elastography score (interquartile range [IQR]) was 5.9 (5.3 to 7.6) kPa, and the mean CD4 count (SD) was 579 (223) cells/µL. The median adherence to HCV medications, assessed by pill count, was 100% (95% confidence interval [CI], 100%-100%), and HIV ranged from 99% to 100% (100%; 95% CI, 90%-100%) over the 7-month study duration. HIV undetectability was maintained in all but 1 participant enrolled with unsuspected multiclass resistance. Treatment was well tolerated, with no study medication modification due to adverse events and no serious adverse event related to the study drug. All participants achieved sustained virological response. The mean CD4 count (SD) increased to 673 (361) cells/µL, and the fibrosis score (IQR) declined to 5.2 (4.4 to 7.4) kPa by week 12 after HCV treatment. There was no treatment effect on glucose metabolism. Cholesterol increased during and after treatment.

Conclusions: Provision of this 2-tablet daily HIV-HCV regimen is feasible, well tolerated, and safe, avoids drug-drug interactions between HIV and HCV medications, maintains HIV suppression in the absence of drug resistance, and is highly curative of HCV.

Keywords: antiviral therapy; cirrhosis; insulin resistance; lipid metabolism; viral hepatitis.