|
Susanna Naggie, M.D., M.H.S., Curtis Cooper, M.D., Michael Saag, M.D., Kimberly Workowski, M.D., Peter Ruane, M.D., William J. Towner, M.D., Kristen Marks, M.D., Anne Luetkemeyer, M.D., Rachel P. Baden, M.D., Paul E. Sax, M.D., Edward Gane, M.D., Jorge Santana-Bagur, M.D., Luisa M. Stamm, M.D., Ph.D., Jenny C. Yang, Pharm.D., Polina German, Pharm.D., Hadas Dvory-Sobol, Ph.D., Liyun Ni, M.A., Phillip S. Pang, M.D., Ph.D., John G. McHutchison, M.D., Catherine A.M. Stedman, M.B., Ch.B., Ph.D., Javier O. Morales-Ramirez, M.D., Norbert Bräu, M.D., Dushyantha Jayaweera, M.D., Amy E. Colson, M.D., Pablo Tebas, M.D., David K. Wong, M.D., Douglas Dieterich, M.D., and Mark Sulkowski, M.D. for the ION-4 Investigators |
|
|
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.)
Supported by Gilead Sciences.
|
|
|