• Anu Osinusi, Kerry Townsend, Anita Kohli, Amy Nelson, Cassie Seamon, Eric G Meissner, Dimitra Bon, Rachel Silk, Chloe Gross, Angie Price, Mohammad Sajadi, Sreetha Sidharthan, Zayani Sims, Eva Herrmann, John Hogan, Gebeyehu Teferi, Rohit Talwani, Michael Proschan, Veronica Jenkins, David E Kleiner, Brad J Wood, G Mani Subramanian, Phillip S Pang, John G McHutchison, Michael A Polis, Anthony S Fauci, Henry Masur, and Shyam Kottilil.
• Division of Infectious Diseases, Institute of Human Virology, University of Maryland, Baltimore2Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland3Gilead Sciences Inc, F.
• JAMA. 2015 Mar 24; 313 (12): 1232-9.

ImportanceThere is an unmet need for interferon- and ribavirin-free treatment for chronic hepatitis C virus (HCV) infection in patients co-infected with human immunodeficiency virus (HIV).ObjectiveTo evaluate the rates of sustained virologic response (SVR) and adverse events in previously untreated patients with HCV genotype 1 and HIV co-infection following a 12-week treatment of the fixed-dose combination of ledipasvir and sofosbuvir.Design, Setting, And ParticipantsOpen-label, single-center, phase 2b pilot study of previously untreated, noncirrhotic patients with HCV genotype 1 and HIV co-infection conducted at the Clinical Research Center of the National Institutes of Health, Bethesda, Maryland, from June 2013 to September 2014. Patients included those receiving antiretroviral therapy with HIV RNA values of 50 copies/mL or fewer and a CD4 T-lymphocyte count of 100 cells/mL or greater or patients with untreated HIV infection with a CD4 T-lymphocyte count of 500 cells/mL or greater. Serial measurements of safety parameters, virologic and host immune correlates, and adherence were performed.InterventionsFifty patients with HCV genotype 1 never before treated for HCV were prescribed a fixed-dose combination of ledipasvir (90 mg) and sofosbuvir (400 mg) once daily for 12 weeks.Main Outcomes And MeasuresThe primary study outcome was the proportion of patients with sustained viral response (plasma HCV RNA level <12 IU/mL) 12 weeks after end of treatment.ResultsForty-nine of 50 participants (98% [95% CI, 89% to 100%]) achieved SVR 12 weeks after end of treatment, whereas 1 patient experienced relapse at week 4 following treatment. In the patient with relapse, deep sequencing revealed a resistance associated mutation in the NS5A region conferring resistance to NS5A inhibitors, such as ledipasvir. The most common adverse events were nasal congestion (16% of patients) and myalgia (14%). There were no discontinuations or serious adverse events attributable to study drug.Conclusions And RelevanceIn this open-label, uncontrolled, pilot study enrolling patients co-infected with HCV genotype 1 and HIV, administration of an oral combination of ledipasvir and sofosbuvir for 12 weeks was associated with high rates of SVR after treatment completion. Larger studies that also include patients with cirrhosis and lower CD4 T-cell counts are required to understand if the results of this study generalize to all patients co-infected with HCV and HIV.Trial Registrationclinicaltrials.gov Identifier:NCT01878799.

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