Treatment of hepatitis C virus (HCV) during the early phase (within 24 weeks of infection) can reduce risk of transmission and lower healthcare costs compared to deferring treatment to the chronic phase.1 Modern oral direct-acting antivirals provide safe and effective treatment for HCV, but their approval is limited to the treatment of chronic infection. Glecaprevir/pibrentasvir (G/P) currently offers the shortest available HCV treatment regimen of eight weeks. Populations that struggle with outpatient medication adherence, such as persons who inject drugs (PWID), may benefit from even shorter treatment courses if proven effective.
A multinational study carried out in 2023 found sustained virologic clearance 12 weeks following treatment completion (SVR12) in 78% of patients given four weeks of G/P.2 The majority of patients were in the early phase of HCV with a median infection duration of 17 weeks. The population was mostly composed of white men who have sex with men (MSM) with concurrent HIV infection. This study was only able to enroll 23 patients due to the COVID-19 pandemic. The authors acknowledged that this study was limited in generalizability due to a small sample size and a limited portion of PWID (30%).
The PURGE-C Study
The PURGE-C study was a phase 2, open-label, single-arm, international (United States and Brazil) trial.3 Eligible participants were adults with confirmed early HCV infection. It could be a first-time infection or reinfection if there was available documented clearance of past HCV. Participants living with HIV (PWH) needed to be on antiretroviral therapy and have a suppressed HIV viral load (HIV-1 RNA <50 copies/mL). Participants were excluded if their HIV treatment had potential drug-drug interactions with G/P, if they had compensated or decompensated cirrhosis, if they had concurrent hepatitis A or B, or if they had other causes of liver disease. Participants were given four weeks of G/P at a fixed dose of 300 mg/120 mg once daily. Study visits occurred at entry and weeks 1, 2, 4 (treatment completion), 8, 12, 16 (SVR12 visit), and 28. The primary objective of this study was occurrence of SVR12.
What You Need to Know
The PURGE-C trial found that a four-week regimen of glecaprevir/pibrentasvir achieved SVR12 in 84% of patients with early hepatitis C infection, indicating that shorter treatment durations may be feasible.
Initiating therapy during the early phase of HCV infection may improve outcomes and support viral clearance before chronic infection develops.
Despite promising results, the study’s small sample size and underrepresentation of persons who inject drugs highlight the need for larger, more diverse trials before routine adoption of abbreviated regimens.
Out of 68 participants screened, 45 were enrolled between November 2019 and January 2023. The median age was 36 and only one patient was female. Participants were predominantly white (51%), followed by Hispanic (31%) and Black (27%). Half of the patients also were HIV positive, and 12 patients (27%) were PWID. The median time from HCV diagnosis to starting G/P was 31 days. The majority (84%) of infections were the participant’s first HCV infection. Median baseline alanine transaminase levels were elevated to 146 U/L and the median HCV RNA was 5.3 log10 IU/mL.
Of the 45 patients with early HCV treated with four weeks of G/P, 38 (84%) achieved SVR12. Out of the seven individuals who experienced treatment failure, six had additional information available. A breakdown of the six evaluable treatment failures is available in Table 1. When looking specifically at PWH, 83% achieved SVR12. Out of the 12 PWID, 9 (75%) achieved SVR12. Most participants (73%) experienced moderate or higher AEs throughout the treatment and screening process, which were often moderate elevations in creatinine or liver inflammation markers, or occurrence of other infections not likely to be related to G/P use. No adverse effects related to the study-treatment led to premature discontinuation.
Any healthcare provider involved in the treatment of HCV has worked with patients who struggle to adhere to their medication. The PURGE-C study contributes to a small body of literature that suggests only four weeks of G/P may be sufficient to treat HCV. PURGE-C also contributes to the evidence that SVR12 rates can be appropriate when treatment is initiated in the early phase.
Only 27% of participants were PWID, again limiting generalizability to a population that is not only highly susceptible to HCV, but also may be facing the highest barriers to medication access. In clinical practice, G/P should still be given for eight weeks as currently indicated, however, if patients are only able to complete four weeks of therapy and are outside the appropriate window to resume, it may be worthwhile to check for SVR12. Otherwise, more robust data will be needed before providers can start suggesting four weeks of G/P for all patients with barriers to adherence.
References
1.Bethea E, Chen Q, Hur C, et al. Should we treat acute hepatitis C? A decision and cost-effectiveness analysis. Hepatology. 2018;67(3):837–846. doi:10.1002/hep.29611.
2.Martinello M, Bhagani S, Shaw D, et al. Glecaprevir-pibrentasvir for 4 weeks among people with recent HCV infection: The TARGET3D study. JHEP Reports. 2023;5(10):100867. doi: 10.1016/j.jhepr.2023.100867.
3.Kim AY, Kang M, Umbleja T, et al. Short course therapy with glecaprevir/pibrentasvir for early Hepatitis C virus infection: PURGE-C. Clin Infect Dis. 2025:ciaf305. doi: 10.1093/cid/ciaf305.
