Background and Objectives
The efficacy of < 12 weeks of hepatitis C virus (HCV) treatment in patients co-infected with HCV and human immunodeficiency virus type 1 (HIV-1) has not been established. We assessed the efficacy and safety of ledipasvir–sofosbuvir for 8 weeks in HCV mono-infected and HCV/HIV-1 co-infected patients.
We enrolled patients mono-infected with genotype 1 HCV or co-infected with HCV and HIV-1 who were HCV treatment-naive and did not have cirrhosis. HCV/HIV-1 co-infected patients were either not receiving antiretroviral treatment and had a CD4 T-cell count > 500 cells/mm3 or were receiving a protocol-approved antiretroviral regimen for ≥ 8 weeks (or ≥ 6 months for abacavir-containing regimens) and had HIV-1 RNA < 50 copies/mL and a CD4 T-cell count > 200 cells/mm3. Patients received ledipasvir–sofosbuvir (90/400 mg) once daily for 8 weeks. The primary efficacy endpoint was sustained virologic response 12 weeks after treatment discontinuation (SVR12).
The SVR12 rate was 100% (67/67) for HCV mono-infected patients and 97% (57/59) for HCV/HIV-1 co-infected patients. Two patients relapsed by the week 4 post-treatment visit. Overall, the most common adverse events were headache (52%) and upper abdominal pain (26%). There were no serious adverse events or treatment discontinuations due to adverse events. No HCV/HIV-1 co-infected patients receiving antiretroviral treatment experienced HIV virologic rebound, and no clinically meaningful changes in CD4 T-cell counts were observed in any co-infected patient.
Non-cirrhotic, treatment-naive patients with genotype 1 HCV mono-infection and HCV/HIV-1 co-infection achieved high rates of SVR12 with 8 weeks of treatment with ledipasvir/sofosbuvir.
ClinicalTrials.gov identifier: NCT02472886.
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Writing assistance was provided by Tiffany DeSimone, PhD, of BlueMomentum, an Ashfield Company, part of UDG Healthcare plc, and was supported and paid for by Gilead Sciences, Inc.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Conflicts of Interest
Vasily Isakov has served on advisory committees or review panels for AbbVie, Bristol-Myers Squibb, Gilead Sciences, Janssen Pharmaceuticals, Merck & Co., R-PHARM, and Vertex Pharmaceuticals. He has also served as a consultant for Bristol-Myers Squibb and Merck & Co., and on speakers’ bureaus for Bristol-Myers Squibb, Janssen Pharmaceuticals, R-PHARM, and Merck & Co. Kathryn Kersey, Sophia Lu, Anu Osinusi, Evguenia Svarovskaia, and Diana M. Brainard are employees and stockholders in Gilead Sciences. Riina Salupere reports personal fees from MSD/Merck, AbbVie, Jannsen, and grants from Intercept outside of the submitted work. Elena Orlova-Morozova has served as a speaker for Janssen-Cilag. Konstantin Zhdanov has served as an investigator for BMS, a speaker and advisor for Abbott, and as an investigator, speaker, and advisor for Gilead, AbbVie, Biocad, Janssen, MSD, Novartis, Roche, and R-Pharm. Natalia Gankina and Viacheslav Morozov have no discloses to declare.
This phase IIIb study (NCT02472886) was sponsored by Gilead Sciences.
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Isakov, V., Gankina, N., Morozov, V. et al. Ledipasvir–Sofosbuvir for 8 Weeks in Non-Cirrhotic Patients with Previously Untreated Genotype 1 HCV Infection ± HIV-1 Co-Infection. Clin Drug Investig 38, 239–247 (2018). https://doi.org/10.1007/s40261-017-0606-0