Ledipasvir and Sofosbuvir for HCV in Patients Coinfected with HIV-1.

Journal Article (Clinical Trial, Phase III;Journal Article;Multicenter Study)

BACKGROUND: Effective treatment for hepatitis C virus (HCV) in patients coinfected with human immunodeficiency virus type 1 (HIV-1) remains an unmet medical need. METHODS: We conducted a multicenter, single-group, open-label study involving patients coinfected with HIV-1 and genotype 1 or 4 HCV receiving an antiretroviral regimen of tenofovir and emtricitabine with efavirenz, rilpivirine, or raltegravir. All patients received ledipasvir, an NS5A inhibitor, and sofosbuvir, a nucleotide polymerase inhibitor, as a single fixed-dose combination for 12 weeks. The primary end point was a sustained virologic response at 12 weeks after the end of therapy. RESULTS: Of the 335 patients enrolled, 34% were black, 55% had been previously treated for HCV, and 20% had cirrhosis. Overall, 322 patients (96%) had a sustained virologic response at 12 weeks after the end of therapy (95% confidence interval [CI], 93 to 98), including rates of 96% (95% CI, 93 to 98) in patients with HCV genotype 1a, 96% (95% CI, 89 to 99) in those with HCV genotype 1b, and 100% (95% CI, 63 to 100) in those with HCV genotype 4. Rates of sustained virologic response were similar regardless of previous treatment or the presence of cirrhosis. Of the 13 patients who did not have a sustained virologic response, 10 had a relapse after the end of treatment. No patient had confirmed HIV-1 virologic rebound. The most common adverse events were headache (25%), fatigue (21%), and diarrhea (11%). No patient discontinued treatment because of adverse events. CONCLUSIONS: Ledipasvir and sofosbuvir for 12 weeks provided high rates of sustained virologic response in patients coinfected with HIV-1 and HCV genotype 1 or 4. (Funded by Gilead Sciences; ION-4 ClinicalTrials.gov number, NCT02073656.).

Full Text

Duke Authors

Cited Authors

  • Naggie, S; Cooper, C; Saag, M; Workowski, K; Ruane, P; Towner, WJ; Marks, K; Luetkemeyer, A; Baden, RP; Sax, PE; Gane, E; Santana-Bagur, J; Stamm, LM; Yang, JC; German, P; Dvory-Sobol, H; Ni, L; Pang, PS; McHutchison, JG; Stedman, CAM; Morales-Ramirez, JO; Bräu, N; Jayaweera, D; Colson, AE; Tebas, P; Wong, DK; Dieterich, D; Sulkowski, M; ION-4 Investigators,

Published Date

  • August 20, 2015

Published In

Volume / Issue

  • 373 / 8

Start / End Page

  • 705 - 713

PubMed ID

  • 26196665

Pubmed Central ID

  • PMC4892372

Electronic International Standard Serial Number (EISSN)

  • 1533-4406

Digital Object Identifier (DOI)

  • 10.1056/NEJMoa1501315


  • eng

Conference Location

  • United States