Ledipasvir and sofosbuvir for HCV in patients coinfected with HIV-1

Susanna Naggie, Curtis Cooper, Michael Saag, Kimberly Workowski, Peter Ruane, William J. Towner, Kristen Marks, Anne Luetkemeyer, Rachel P. Baden, Paul E. Sax, Edward Gane, Jorge Santana-Bagur, Luisa M. Stamm, Jenny C. Yang, Polina German, Hadas Dvory-Sobol, Liyun Ni, Phillip S. Pang, John G. McHutchison, Catherine A.M. StedmanJavier O. Morales-Ramirez, Norbert Bräu, Dushyantha Jayaweera, Amy E. Colson, Pablo Tebas, David K. Wong, Douglas Dieterich, Mark Sulkowski

Research output: Contribution to journalArticle

317 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)705-713
Number of pages9
JournalNew England Journal of Medicine
Volume373
Issue number8
DOIs
StatePublished - Aug 20 2015

ASJC Scopus subject areas

  • Medicine(all)

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    Naggie, S., Cooper, C., Saag, M., Workowski, K., Ruane, P., Towner, W. J., Marks, K., Luetkemeyer, A., Baden, R. P., Sax, P. E., Gane, E., Santana-Bagur, J., Stamm, L. M., Yang, J. C., German, P., Dvory-Sobol, H., Ni, L., Pang, P. S., McHutchison, J. G., ... Sulkowski, M. (2015). Ledipasvir and sofosbuvir for HCV in patients coinfected with HIV-1. New England Journal of Medicine, 373(8), 705-713. https://doi.org/10.1056/NEJMoa1501315