Eight weeks of hepatitis C therapy matched 12 in a large Indian trial

A two-month course of the hepatitis C combination pill sofosbuvir–velpatasvir cured infection about as reliably as the standard three-month course in adults without cirrhosis, according to RESOLVE, a randomised trial run in India's public hospitals [s1]. If the shorter regimen is adopted, it would cut a third off the drug bill for each patient treated — a meaningful number for the national elimination programmes that account for most hepatitis C treatment worldwide [s1].

Hepatitis C is a curable viral infection of the liver; direct-acting antivirals clear it in the large majority of patients, and sofosbuvir–velpatasvir is a pan-genotypic combination usually given for 12 weeks to people without cirrhosis [s1]. The question RESOLVE set out to answer was whether eight weeks would do just as well in the many patients caught before the liver is scarred [s1].

The stakes are practical rather than scientific. Direct-acting antivirals already cure the great majority of hepatitis C, so there is little room to improve on efficacy; the lever left to pull is cost and duration, which govern how many people a fixed budget can treat. Shorter courses also tend to mean fewer clinic visits and less chance of a patient dropping out before cure — both of which matter in the high-volume public programmes that carry most of the global treatment load [s1].

What the trial did

RESOLVE was a multicentre, open-label, non-inferiority trial conducted at five publicly funded hospitals in India and funded by the Indian Council of Medical Research and the Government of India's Department of Health Research [s1]. Treatment-naive adults aged 18 or older with non-cirrhotic hepatitis C mono-infection were randomly assigned 1:1 to sofosbuvir 400 mg plus velpatasvir 100 mg once daily for either eight or 12 weeks [s1][s2]. The primary endpoint was sustained virological response — no quantifiable HCV RNA 12 weeks after treatment ended (SVR12), the standard definition of cure — assessed in the per-protocol population [s1]. The trial assumed the 12-week regimen would cure 95% of patients and was designed with a 5% non-inferiority margin, a one-sided alpha of 2.5% and 90% power — meaning it was built to detect whether the shorter course fell meaningfully short of that near-ceiling cure rate [s1].

Between 15 May 2022 and 10 September 2024, 1620 people were screened and 880 (54.3%) enrolled: 437 (50%) assigned to the 12-week course and 443 (50%) to the eight-week course [s1]. Just over half, 455 (52%), were women, and the median age was 35 years [s1]. In all, 816 (93%) completed treatment and SVR12 testing, split evenly between the arms [s1].

What it found

In the per-protocol analysis, 410 of 415 patients on the eight-week course reached SVR12 — 98.8% (95% confidence interval 97.2–99.6) — against 397 of 401 on the 12-week course, or 99.0% (97.5–99.7) [s1]. The risk difference was 0.2 percentage points (95% confidence interval −1.5 to 1.9), comfortably inside the pre-set 5% margin, so the shorter course was declared non-inferior [s1].

The more conservative intention-to-treat analysis, which counts everyone randomised, pointed the same way: 414 of 443 (93.5%; 90.9–95.5) with eight weeks versus 401 of 437 (91.8%; 88.8–94.2) with 12 weeks, a risk difference of −1.7 percentage points (−5.2 to 1.9) [s1]. No participant had a drug-related serious adverse event or stopped treatment because of a side-effect [s1].

How to read it

Non-inferiority is exactly the right frame here: the 12-week regimen already cures almost everyone, so the useful question is whether a cheaper, shorter course sacrifices any of that, and RESOLVE's answer is that it does not within the margin tested [s1]. The limits are specific and worth stating. The trial enrolled only treatment-naive, non-cirrhotic adults without HIV co-infection, so the result does not extend to people with cirrhosis, prior treatment failure or co-infection, who are not candidates for shortening [s1]. It was open-label and conducted in one country's health system, though SVR12 is an objective laboratory endpoint that resists bias [s1].

Because the trial was publicly funded rather than run by the drug's manufacturer, it addresses a question — can we treat for less? — that industry-sponsored trials rarely pose [s1]. The reassuringly clean safety record, with no drug-related serious adverse events and no discontinuations for side-effects in either arm, reflects how well tolerated this combination already is and removes safety as an argument against the shorter course [s1].

What to watch

Whether guideline committees and national programmes move to an eight-week default for this patient group, and whether real-world adherence outside a trial setting holds the cure rate as high [s1]. This article describes research and is not medical advice.

Sources

• 8 weeks versus 12 weeks of sofosbuvir–velpatasvir for chronic hepatitis C (RESOLVE) — The Lancet, 30 September 2026
• RESOLVE trial registration, CTRI/2022/03/041368 — Clinical Trials Registry — India