An estimated 69,000 Americans acquired hepatitis C in 2023, roughly double the mid-2010s rate, even though the disease has been curable with an eight- to 12-week course of oral antivirals for more than a decade. AbbVie’s MAVYRET became the first of those antivirals cleared for acute infection in June 2025, with a 96% cure rate in trial. In the EU, the drug, billed as MAVIRET, won extended approval to treat acute hepatitis C virus infections in June 2026.
Maviret box. Image credit: AbbVie
It is clear that the drug, which is comprised of the antivirals glecaprevir and pibrentasvir, works. Months after both approvals, the question now is whether the treatment is reaching the patients most susceptible to recurrent infections.
“If treated early with safe and effective therapies, providers can cure virtually all patients with hepatitis C before it escalates to chronic disease,” John Ward, director of the Coalition for Global Hepatitis Elimination, said in an AbbVie press release. Treatments for HCV have existed since 1991, when the FDA approved an alpha interferon injection, which had a viral eradication rate of only about 10%.
The efficacy has increased by nearly an order of magnitude since then. The Phase 3 trial that evaluated AbbVie’s Maviret, a direct-acting antiviral that targets HCV, showed a sustained virologic response rate (SVR) of 96.2% at 12 weeks in the intention-to-treat population and 100% in the modified intention-to-treat population excluding non-virologic failures, with no on-treatment virologic failures or post-treatment relapses.
Maviret was approved by the EU for chronic HCV in 2017, followed by FDA approval six days later. Last year, the FDA approved a label expansion to include acute HCV. The EU approved the same expansion in June of this year.
“Before the acute indication, patients could be required to wait for confirmation of chronicity, even though current clinical guidelines support treatment as soon as acute infection is diagnosed. That delay can add unnecessary visits, create administrative barriers and, most importantly, increase the risk that patients disengage from care. Such delays may allow continued transmission and hamper HCV elimination efforts,” Ivan Gentile, an infectious disease specialist at the University of Naples Federico II and co-author of the trial results, said in an email to Drug Discovery and Development.
Approximately 18% of the participants in the Phase 3 trial that evaluated Maviret for acute HCV were being treated for at least their second HCV infection and nearly 40% of those had two or more prior infections. Two participants had six prior infections. Among those with recurrent infections, the most common prior treatment was Maviret itself.
“The study found that a history of prior HCV infection did not appear to affect the [SVR]. Moreover, no virologic failures were observed in the study, including among participants who had previously received [Maviret] for an earlier infection. These findings suggest that neither prior infection nor previous exposure to the same regimen compromised the virologic response to treatment of the current episode,” Gentile said.
He noted that these findings are especially relevant for patients at high risk of reinfection, including people who inject drugs and those with ongoing sexual exposure risk.
A systematic review of 36 studies covering 6,311 person-years, a metric that sums to total years individuals spend under observation, of follow-up found an overall reinfection rate of 5.9 per 100 person-years among people with recent drug use. Comparatively, general reinfection rates for HCV are approximately 1.27 per 100 person-years.
“Antiviral treatment does not modify the underlying exposure,” Gentile said. “Repeated treatment must therefore be integrated into a broader prevention strategy, including harm-reduction services, access to sterile injecting equipment, treatment for substance-use disorders when appropriate, sexual-health interventions, regular HCV RNA testing and rapid retreatment following reinfection.”
“Reinfection should not be seen as a reason to delay or even withhold therapy, but as a signal that treatment and prevention services need to be delivered together. From an elimination perspective, people with repeated infections may actually be among those for whom rapid treatment has the greatest potential individual and public-health value,” he added.
“This study provides strong evidence of antiviral efficacy, but it does not fully answer the question of effectiveness in populations that are least engaged in care,” Gentile said.
Only 14.3% of participants in the Phase 3 trial were classified as people who currently or recently injected drugs. Almost 50% of the participants had HIV, but all of them were receiving antiretroviral therapy, meaning they were connected to the healthcare system.
These factors may have contributed to the trial’s low dropout rate and could limit how well the results generalize to people who aren’t regularly engaged in care, Gentile said. Data about people who are unconnected or have an unstable connection to the healthcare system is growing but remains limited, he added.
The next step is to determine how treatment can be delivered to harder to reach populations, Gentile said. Studies should include data such as the proportion of participants diagnosed who began treatment, time from diagnosis to first dose, treatment completion, loss to follow-up, documented SVR, reinfection and successful retreatment after reinfection, he said.
For Gentile, Maviret’s label expansion in the EU marks a step towards translating clinical results to the real world.
“The acute indication provides a valuable tool in this context because it removes one practical barrier: clinicians no longer need to wait for confirmation of chronicity or rely on off-label prescribing before initiating treatment,” he said.
