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Is 4 Weeks of Glecaprevir/Pibrentasvir Sufficient to Treat Early Hepatitis C Infection?

Treatment of hepatitis C virus (HCV) during the early phase (within 24 weeks of infection) can reduce risk of transmission and lower health care costs compared with 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 8 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.

Results from a multinational study carried out in 2023 found sustained virologic clearance 12 weeks following treatment completion (SVR12) in 78% of patients given 4 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 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 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 4 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.

Of 68 participants screened, 45 were enrolled between November 2019 and January 2023. The median age was 36 years, and only 1 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 4 weeks of G/P, 38 (84%) achieved SVR12. Of the 7 individuals who experienced treatment failure, 6 had additional information available. A breakdown of the 6 evaluable treatment failures is available here. When looking specifically at PWH, 83% achieved SVR12. Of the 12 PWID, 9 (75%) achieved SVR12. Most participants (73%) experienced moderate or higher adverse effects (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 AEs 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 8 weeks as currently indicated; however, if patients are only able to complete 4 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 4 weeks of G/P for all patients with barriers to adherence.

By Devin Donnelly, PharmD, AAHIVP, BCIDP

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

Source: Contagion Live