Background: The pangenotypic, once-daily combination of daclatasvir (DCV) and sofosbuvir (SOF) achieves high rates of sustained virologic response (SVR) in patients with chronic HCV infection. DCV+SOF has favorable safety and drug-drug interaction profiles and a high barrier to resistance, supporting the phase 3 ALLY-2 study of DCV+SOF in patients with HIV/HCV coinfection.
Methods: This randomized, open-label study enrolled HCV treatment-naive (N=151) or experienced (N=52) adults coinfected with HIV and HCV (any genotype). Naive patients were randomly assigned (2:1), with stratification by cirrhosis status and HCV GT, to receive 12 or 8 weeks of once-daily SOF 400mg + DCV 60mg (dose-adjusted for concomitant antiretrovirals: 30mg with ritonavir-boosted PIs, 90mg with NNRTIs except rilpivirine). Experienced patients received this same regimen for 12 weeks. The primary endpoint was HCV RNA < LLOQ (25 IU/mL) at posttreatment Week 12 (SVR12) in naive GT1 patients treated for 12 weeks.
Results: Treatment arms were well balanced with a median age of 52 y, 87% male, and 62% white/34% black. 83%, 9%, 6%, and 2% of patients, respectively, had GT1, 2, 3, and 4 infection; median baseline HCV RNA was 6.7 log10 IU/mL; 14% had cirrhosis. The median baseline CD4 count was 565 cells/μL and 94% had HIV RNA <50 cp/mL. 99, 50, and 50 patients, respectively, received PI-based, NNRTI-based, or other (primarily INI-based) cART; 4 patients did not receive cART. 199/203 (98%) patients completed therapy; 2 patients discontinued early for noncompliance and 2 for incarceration. Overall, SVR12 was achieved by 97% and 98% of naive and experienced patients, respectively, after 12 weeks of therapy, and by 76% of naive patients after 8 weeks (Table). Among patients treated for 12 weeks, SVR12 rates were similar regardless of prior treatment experience, HCV GT or GT1 subtype, cirrhosis status, concurrent cART regimen, or race. There were no virologic breakthroughs; 2/153 patients (1%) in the 12-week group and 10/50 (20%) in the 8-week group had posttreatment relapse. There were no treatment-related serious AE or AE leading to discontinuation. Treatment-emergent grade 3/4 lab abnormalities included increases in INR (2 patients), AST (1), total bilirubin (8, all received ATV/r), and lipase (7, all transient without pancreatitis).
Conclusions: DCV+SOF once daily for 12 weeks achieved SVR12 in 97% of patients coinfected with HIV and HCV GT1, 2, 3, or 4, and was safe and well-tolerated.