Ledipasvir–Sofosbuvir for 8 Weeks in Non-Cirrhotic Patients with Previously Untreated Genotype 1 HCV Infection ± HIV-1 Co-Infection

A Correction to this article is available

This article has been updated


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.

This is a preview of subscription content, access via your institution.

Fig. 1

Change history


  1. 1.

    Saraswat V, Norris S, de Knegt RJ, Sanchez Avila JF, Sonderup M, Zuckerman E, et al. Historical epidemiology of hepatitis C virus (HCV) in select countries—volume 2. J Viral Hepat. 2015;22(Suppl 1):6–25.

    Article  PubMed  Google Scholar 

  2. 2.

    Messina JP, Humphreys I, Flaxman A, Brown A, Cooke GS, Pybus OG, et al. Global distribution and prevalence of hepatitis C virus genotypes. Hepatology. 2015;61(1):77–87.

    Article  PubMed  Google Scholar 

  3. 3.

    Liakina V, Hamid S, Tanaka J, Olafsson S, Sharara AI, Alavian SM, et al. Historical epidemiology of hepatitis C virus (HCV) in select countries—volume 3. J Viral Hepat. 2015;22(Suppl 4):4–20.

    Article  PubMed  Google Scholar 

  4. 4.

    Tallo T, Norder H, Tefanova V, Krispin T, Schmidt J, Ilmoja M, et al. Genetic characterization of hepatitis C virus strains in Estonia: fluctuations in the predominating subtype with time. J Med Virol. 2007;79(4):374–82.

    Article  PubMed  Google Scholar 

  5. 5.

    Korolevskaya LB, Shmagel KV, Saidakova EV, Shmagel NG, Slobodchikova SV, Chereshnev VA. Effect of hepatitis c virus coinfection on the content of CD4(+) and CD8(+) T Cell subpopulations in HIV-infected patients receiving antiretroviral therapy. Bull Exp Biol Med. 2016;161(2):281–3.

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Isakov V, Zhdanov K, Kersey K, Svarovskaia E, Massetto B, Zhu Y, et al. Efficacy of sofosbuvir plus ribavirin in treatment-naive patients with genotype 1 and 3 HCV infection: results from a Russian phase IIIb study. Antivir Ther. 2016;21(8):671–8.

    Article  PubMed  Google Scholar 

  7. 7.

    Soriano V, Labarga P, Fernandez-Montero JV, et al. Drug interactions in HIV-infected patients treated for hepatitis C. Expert Opin Drug Metab Toxicol. 2017;13:807–16.

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Lam AM, Murakami E, Espiritu C, Steuer HM, Niu C, Keilman M, et al. PSI-7851, a pronucleotide of beta-D-2’-deoxy-2’-fluoro-2’-C-methyluridine monophosphate, is a potent and pan-genotype inhibitor of hepatitis C virus replication. Antimicrob Agents Chemother. 2010;54(8):3187–96.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Lawitz EJ, Gruener D, Hill JM, Marbury T, Moorehead L, Mathias A, et al. A phase 1, randomized, placebo-controlled, 3-day, dose-ranging study of GS-5885, an NS5A inhibitor, in patients with genotype 1 hepatitis C. J Hepatol. 2012;57(1):24–31.

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Gilead Sciences, Inc. HARVONI (ledipasvir and sofosbuvir) prescribing information. Foster City: Gilead Sciences, Inc.; 2016.

    Google Scholar 

  11. 11.

    Gilead Sciences International Ltd. HARVONI (ledipasvir/sofosbuvir) summary of product characteristics. Cambridge: Gilead Sciences International Ltd; 2016.

    Google Scholar 

  12. 12.

    Naggie S, Cooper C, Saag M, Workowski K, Ruane P, Towner WJ, et al. Ledipasvir and sofosbuvir for HCV in patients coinfected with HIV-1. N Engl J Med. 2015;373(8):705–13.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Neukam K, Morano-Amado LE, Rivero-Juárez A, et al. HIV-coinfected patients respond worse to direct-acting antiviral-based therapy against chronic hepatitis C in real life than HCV-monoinfected individuals: a prospective cohort study. HIV Clin Trials. 2017;18:126–34.

    Article  PubMed  Google Scholar 

  14. 14.

    Arias A, Aguilera A, Soriano V, et al. Rate and predictors of treatment failure to all-oral HCV regimens outside clinical trials. Antiviral Ther. 2017;22:307–12.

    Article  Google Scholar 

  15. 15.

    Kowdley KV, Gordon SC, Reddy KR, Rossaro L, Bernstein DE, Lawitz E, et al. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N Engl J Med. 2014;370(20):1879–88.

    Article  PubMed  Google Scholar 

  16. 16.

    Backus LI, Belperio PS, Shahoumian TA, Loomis TP, Mole LA. Real-world effectiveness of ledipasvir/sofosbuvir in 4,365 treatment-naive, genotype 1 hepatitis C-infected patients. Hepatology. 2016;64(2):405–14.

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Younossi ZM, Park H, Gordon SC, Ferguson JR, Ahmed A, Dieterich D, et al. Real-world outcomes of ledipasvir/sofosbuvir in treatment-naive patients with hepatitis C. Am J Manag Care. 2016;22(6 Spec No.):SP205–11.

    PubMed  Google Scholar 

  18. 18.

    Ingiliz P, Christensen S, Kimhofer T, Hueppe D, Lutz T, Schewe K, et al. Sofosbuvir and Ledipasvir for 8 weeks for the treatment of chronic hepatitis C virus infection in HCV-mono-infected and HIV-HCV co-infected individuals—results from the German hepatitis C cohort (GECCO-01). Clin Infect Dis. 2016;63(10):1320–4.

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Ain D, Wolfe P, Weissman M, et al. Ledipasvir/sofosbuvir for 8 weeks in patients co-infected with HCV and HIV-1. In: Presented at HEP DART, December 2015, Wailea, HI.

  20. 20.

    Wyles DL, Ruane PJ, Sulkowski MS, Dieterich D, Luetkemeyer A, Morgan TR, et al. Daclatasvir plus sofosbuvir for HCV in patients coinfected with HIV-1. N Engl J Med. 2015;373(8):714–25.

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Sulkowski M, Hezode C, Gerstoft J, Vierling JM, Mallolas J, Pol S, et al. Efficacy and safety of 8 weeks versus 12 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin in patients with hepatitis C virus genotype 1 mono-infection and HIV/hepatitis C virus co-infection (C-WORTHY): a randomised, open-label phase 2 trial. Lancet. 2015;385(9973):1087–97.

    CAS  Article  PubMed  Google Scholar 

  22. 22.

    Rockstroh JK, Nelson M, Katlama C, Lalezari J, Mallolas J, Bloch M, et al. Efficacy and safety of grazoprevir (MK-5172) and elbasvir (MK-8742) in patients with hepatitis C virus and HIV co-infection (C-EDGE CO-INFECTION): a non-randomised, open-label trial. Lancet HIV. 2015;2(8):e319–27.

    Article  PubMed  Google Scholar 

  23. 23.

    Wyles D, Pockros P, Morelli G, Younes Z, Svarovskaia E, Yang JC, et al. Ledipasvir–sofosbuvir plus ribavirin for patients with genotype 1 hepatitis C virus previously treated in clinical trials of sofosbuvir regimens. Hepatology. 2015;61(6):1793–7.

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Afdhal N, Zeuzem S, Kwo P, Chojkier M, Gitlin N, Puoti M, et al. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014;370(20):1889–98.

    Article  PubMed  Google Scholar 

  25. 25.

    Afdhal N, Reddy KR, Nelson DR, Lawitz E, Gordon SC, Schiff E, et al. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med. 2014;370(16):1483–93.

    CAS  Article  PubMed  Google Scholar 

Download references


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.

Author information




KK, AO, ES, and DB contributed to the study concept and design. All investigators collected data, and all authors contributed to data analysis/interpretation and to drafting or critically revising the manuscript. All authors approved the final version of the article.

Corresponding author

Correspondence to Vasily Isakov.

Ethics declarations

Ethical Approval

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.

Financial Support

This phase IIIb study (NCT02472886) was sponsored by Gilead Sciences.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 37 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

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

Download citation