Shorter-course treatment with combinations of three or four different direct-acting antiviral agents achieved sustain viral response in 12 weeks (SVR12) in less than a third of patients with hepatitis C virus infection in an open-label, non-randomized, phase 2a proof-of-concept study.
SVR12 was achieved in 10 of 25 (40%) treatment-naive patients without cirrhosis who were treated with a 3-drug regimen consisting of ledipasvir and sofosbuvir plus GS-9451 (an NS3/4A protease inhibitor) for 4 weeks, and in 5 of 25 (20%) of 25 treatment-naive patients without cirrhosis treated with ledipasvir and sofosbuvir plus GS9451 and GS-9669 (a nonnucleoside NS5B polymerase inhibitor) for 4 weeks, Dr. Anita Kohli of the National Institutes of Health Clinical Center, Bethesda, Md. and her colleagues reported Nov. 23 in Annals of Internal Medicine.
“Given the high cost of DAAs, the medical care required, and the improvements in patient adherence with reductions in treatment duration, attempts to evaluate shorter courses of therapy could have important clinical and public health implications,” Dr. Kohli noted.
Courtesy NIH
Lower baseline HCV viral load, younger age, and HCV genotype 1b were associated with SVR12 with this shortened (vs. the usual 6 weeks) course of direct-acting antiviral (DAA) therapy. Adverse events were mainly mild fatigue, diarrhea, and headaches occurring in 48% and 72% of patients in the 3- and 4-drug regimen groups, respectively, Dr. Kohli said (Ann Intern Med. 2015 Nov. 23[doi:10.7326/M15-0642).
“Sixty-eight percent (34 of 50) of patients had viral relapse, the majority (68%) by posttreatment week 4. Thus, a treatment duration of 4 weeks with 3 or 4 potent DAAs is not sufficient to cure HCV infection in most patients,” she wrote, noting, however, that “some patients are capable of achieving SVR with 4 weeks of therapy, which could be attributable to the presence of several favorable factors, such as early fibrosis, low viral burden, and absence of [resistance-associated variants].
This study was funded in part by the NIH and the German Research Foundation. Study medications were provided by Gilead Sciences. Dr. Kohli reported having no other disclosures. Multiple authors reported other disclosures, including employment and/or stock ownership with Gilead Sciences, research and other funding from Gilead Sciences, and/or stock ownership in Merck, Pfizer, and Johnson & Johnson.