Background : The all-oral, pangenotypic, once-daily combination of daclatasvir (DCV) and sofosbuvir (SOF) for 12 weeks achieved a sustained virologic response (SVR) of 97% in HCV/HIV coinfected subjects. SOF+DCV was well-tolerated and had a favorable drug interaction profile across a broad range of HIV combination antiretroviral therapy (cART). Black race has historically been associated with lower response rates to interferon-based HCV treatment.
Methods: In the open-label ALLY-2 study, HCV/HIV coinfected subjects received either 8 or 12 weeks of once-daily SOF 400mg + DCV 60mg (with dose adjustment for cART: 30mg with ritonavir-boosted PIs, 90mg with NNRTIs except rilpivirine [60mg]). This sub-analysis evaluated efficacy and safety of DCV+SOF in the 50 black subjects who received 12 weeks of therapy.
Results: The majority of black subjects were male (84%), non-cirrhotic (76%) and IL28B non-CC (84%). Median baseline HCV RNA was 6.68 (5.2–7.8) log10 IU/mL and median CD4 count was 551 cells/mm3. SVR12 was 98% (49/50) and 97% (100/103) among black and non-black subjects, respectively. Among black subjects, high SVR12 rates were observed independent of age, gender, cirrhosis status, IL28B genotype, cART regimen, HCV genotype, baseline HCV RNA, or baseline CD4 count (Table). SVR12 was 100% among subjects who had IL28B TT genotype (22/22), received efavirenz (11/11), and who were HCV treatment-naive (30/30). SVR12 was 95% (19/20) among HCV treatment-experienced subjects; the only subject who did not achieve SVR12 had HCV GT 1a, cirrhosis, and high baseline HCV viral load (≥1x107 IU/mL). No treatment-related serious adverse events (AEs) or AEs leading to discontinuation were observed. Grade 1–4 AEs were similar between naive and experienced groups and consistent with the known safety profiles of DCV+SOF; AEs >10% were headache and fatigue. Grade 3/4 laboratory abnormalities were elevations in lipase (n=3), INR in a patient on anticoagulation therapy, and total bilirubin in a patient on atazanavir/ritonavir. There were no grade 3/4 changes in creatinine.
once daily for 12 weeks was highly efficacious and well-tolerated in black subjects
with HCV/HIV coinfection, regardless of baseline factors.
A. Mills, Bristol-Myers Squibb: Grant Investigator , Grant recipient
Gilead: Grant Investigator , Grant recipient
Viiv: Grant Investigator , Grant recipient
Merck: Grant Investigator , Grant recipient
Y. Zhao, Bristol-Myers Squibb: Employee , Salary
S. Noviello, Bristol Myers Squibb: Employee , Salary
Merck/Schering-Plough: Employee and Shareholder , Salary
J&J: Shareholder , Stocks
P. Ackerman, Bristol Myers Squibb: Employee , Salary