Background Direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection has resulted in high rates of disease cure; however, not enough specialists currently are available to provide care. Objective To determine the efficacy of HCV treatment independently provided by nurse practitioners (NPs), primary care physicians (PCPs), or specialist physicians using DAA therapy. Design Nonrandomized, open-label clinical trial initiated in 2015. (ClinicalTrials.gov: NCT02339038) Setting 13 urban, federally qualified health centers (FQHCs) in the District of Columbia. Patients A referred sample of 600 patients, of whom 96% were black, 69% were male, 82% were treatment naive, and 20% had cirrhosis. Seventy-two percent of the patients had HCV genotype 1a infection. The baseline characteristics of patients seen by each provider type were similar. Intervention Patients were assigned in a nonrandomized but specified manner to receive treatment from 1 of 5 NPs, 5 PCPs, or 6 specialists. All providers underwent an identical 3-hour training session based on guidelines. Patients received treatment with ledipasvir–sofosbuvir, which was provided on site, according to U.S. Food and Drug Administration labeling requirements. Measurements Sustained virologic response (SVR). Results 516 patients achieved SVR, a response rate of 86% (95% CI, 83.0% to 88.7%), with no major safety signals. Response rates were consistent across the 3 provider types: NPs, 89.3% (CI, 83.3% to 93.8%); PCPs, 86.9% (CI, 80.6% to 91.7%); and specialists, 83.8% (CI, 79.0% to 87.8%). Patient loss to follow-up was the major cause of non-SVR. Limitation Nonrandomized patient distribution; possible referral bias. Conclusion In a real-world cohort of patients at urban FQHCs, HCV treatment administered by nonspecialist providers was as safe and effective as that provided by specialists. Nurse practitioners and PCPs with compact didactic training could substantially expand the availability of community-based providers to escalate HCV therapy, bridging existing gaps in the continuum of care for patients with HCV infection. Primary Funding Source National Institutes of Health and Gilead Sciences.

clinicaltrials.gov Identifier:NCT01878799.

Background Direct acting anti-HCV drugs have demonstrated a high cure rate and favorable tolerability. The development of shorter courses of therapy may improve affordability and adherence. Sofosbuvir and ledipasvir together with ribavirin have yielded high efficacy when administered for 8, but not for 6 weeks. We hypothesized that addition of a third potent directly acting antiviral to sofosbuvir and ledipasvir would allow for shortened durations of therapy. Methods In this single center, open-label cohort, phase 2 atrial, sixty HCV GT-1 treatment naïve patients were sequentially enrolled onto three arms and treated with 12 weeks of sofosbuvir and ledipasvir (an NS5B nucleotide polymerase inhibitor and an NS5A inhibitor, respectively) (n=20); or 6 weeks with sofosbuvir, ledipasvir, and GS-9669 (a non-nucleoside NS5B inhibitor) (n=20) or 6 weeks with sofosbuvir, ledipasvir and GS-9451 (an NS3/4A protease inhibitor) (n=20). Patients and investigators were unmasked to treatment assignment. The primary efficacy analysis was SVR12 (HCV RNA less than the level of quantitation 12 weeks after treatment completion). Findings All subjects treated with sofosbuvir and ledipasvir for 12 weeks achieved SVR12 (95%CI: 83–100%). Nineteen of 20 patients (95% CI: 75–100%) treated with sofosbuvir, ledipasvir and GS-9669 achieved SVR12, with 1 patient relapsing 2 weeks after completion of therapy. Nineteen of 20 patients (95% CI: 75–100%) treated with sofosbuvir, ledipasvir, and GS-9451 for 6 weeks achieved SVR12, one patient was lost to follow up after achieving SVR4. There were no discontinuations of treatment due to adverse events. Interpretation In this small proof of concept study, two different three drug regimens administered for 6 weeks resulted in high cure rates for HCV infection with excellent tolerability. Funding NIAID, National Cancer Institute and Clinical Center Intramural Program. Clinical Trials.gov number NCT01805882. The study was also supported in part by the German Research Foundation (DFG) by the clinical research unit KFO 129 and a Collaborative Research and Development Agreement between NIH and Gilead Sciences.