In the treatment or non-cirrhotic patients with chronic hepatitis C virus (HCV) infection, an 8-week course of sofosbuvir–velpatasvir combination has similar efficacy to the standard 12-week course, according to the open-label RESOLVE trial.
The primary outcome of sustained virological response, defined as the absence of quantifiable HCV RNA at 12 weeks (SVR12), was achieved in 98.8 percent of patients in the 8-week treatment group vs 99 percent of those in the 12-week treatment group on per-protocol analysis. Results were similar on intention-to-treat (ITT) analysis, with SVR12 met in 93.5 percent of patients in the 8-week treatment group vs 91.8 percent of those in the 12-week treatment group. [Lancet 2026;408:1593-1602]
The corresponding risk difference was 0.2 percent (95 percent confidence interval [CI], −1.5 to 1.9) on per-protocol analysis and –1.7 percent (95 percent CI, −5.2 to 1.9) on ITT analysis, with the upper bound of the 95 percent CI being less than the predefined noninferiority margin of 5 percent, establishing the noninferiority of shortened treatment course.
Subgroup analyses also showed the noninferiority of the 8-week treatment course to the 12-week treatment course among the following:
Patients with genotype 3 HCV (risk differences, −0.6 percent, 95 percent CI, −2.5 to 1.1 on per-protocol analysis and −2.6 percent, 95 percent CI, −6.6 to 1.2 on ITT analysis)
Patients with F2 or F3 fibrosis (risk differences, 0.7 percent, 95 percent CI, −0.7 to 2.1 on per-protocol analysis and –2.3 percent, 95 percent CI, −7.5 to 2.9 on ITT analysis)
Patients with F0 or F1 fibrosis (risk difference, 0.4 percent, 95 percent CI, −2.1 to 3.0 on per-protocol analysis)
There were no reports of drug-related serious adverse event (AE) or drug discontinuation due to an AE. One patient in the 12-week treatment group died of suspected myocardial infarction 2 weeks after treatment completion, and this death was deemed unrelated to the study drug.
“The findings support shortening the duration of sofosbuvir–velpatasvir combination treatment in patients with chronic HCV infection but without cirrhosis,” said first author Dr Amit Goel from Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India, and colleagues.
Goel and colleagues emphasized that shortening the duration of direct-acting antiviral (DAA) treatments could lead to improved compliance and treatment completion and reduced cost.
“Shorter treatment would also be advantageous for public health programmes offering HCV treatment, especially in resource-constrained regions, through reduced per capita expenditure on drugs as well as logistical advantages, such as the need for fewer patient visits,” they added.
In a linked commentary, Drs Marianne Martinello and Gregory Dore from the University of New South Wales, Sydney, Australia, echoed Goel and colleagues, saying, “Shortened duration direct-acting antiviral treatment … may be particularly important in resource-limited settings where procurement costs remain a barrier despite availability of generic DAA therapy. [Lancet 2026;408:1532-1533]
“RESOLVE answered a question important to clinical medicine and public health with findings that have relevance for people with HCV infection, clinicians, and policy makers, particularly in resource-limited settings,” they added.
However, Martinello and Dore pointed out that the trial excluded people who would traditionally be considered at risk of treatment discontinuation or who might find treatment completion more difficult, such as people who inject drugs.
That said, the “efficacy and so-called therapeutic forgiveness” of shortened DAA treatment course in less engaged populations remained unaddressed, they said. “Populations most likely to benefit from shortened therapy must be included in future research.”
RESOLVE included 880 treatment-naïve adult patients with non-cirrhotic HCV mono-infection. These patients were randomly assigned to receive sofosbuvir 400 mg plus velpatasvir 100 mg orally once daily for either 8 weeks (n=443) or 12 weeks (n=437). The per-protocol analysis included 816 patients (median age 35 years, 52 percent female), while the ITT analysis included 880.
Overall, nine patients, including four in the 12-week treatment group and five in the 8-week treatment group, did not attain SVR12 on per-protocol analysis. Of these patients, six had genotype 3 infection.