Background:
Glecaprevir-pibrentasvir for eight weeks is recommended for treatment of chronic HCV infection and in recent infection has been shown to be highly effective as a six-week regimen. Shortened treatment duration may assist in elimination efforts among key populations. The aim of this analysis was to evaluate the efficacy of glecaprevir-pibrentasvir for four weeks in people with recent HCV infection.
Methods:
In this open-label single-arm multi-centre international pilot study, adults with recent HCV infection (duration of infection < 12 months) received glecaprevir-pibrentasvir 300mg-120mg daily for four weeks. Recent primary infection was defined by first positive anti-HCV antibody and/or HCV RNA within six months of enrolment and either acute clinical hepatitis within the past 12 months (symptomatic seroconversion illness or ALT > 10 X ULN), or anti HCV antibody seroconversion within 18 months. Recent re-infection was defined as a new positive HCV RNA within six months of enrolment and evidence of prior spontaneous or treatment induced clearance. The primary endpoint was sustained virological response at 12 weeks post-treatment (SVR12).
Results:
Twenty three participants (96% men, median age 46 years) received treatment, of whom 70% (n=16) had HIV, 57% (n=13) had ever injected drugs, and 35% (n=8) had recent reinfection. The majority had HCV genotype 1 infection (74%) followed by genotypes 3 (9%), 4 (9%) and 2 (4%). At baseline median estimated duration of infection was 7 weeks (IQR 11,29) and median HCV RNA was 5.8 log 10 IU/ml (range 4, 7.5). Virological suppression at week two and week four (end of treatment) was seen in 65% (15/23) and 87% (20/23) respectively. SVR12 in the intent-to-treat and per-protocol populations was achieved in 78% (18/23; 95% CI 56%,93%) and 82% (18/22; 95% CI 60%,95%) respectively. There were four cases of virological failure (all confirmed as relapse by sequencing), 3 genotype 1 and 1 genotype 4d. Median baseline HCV RNA in relapsers was 7.3 log 10 IU/ml. Adherence was suboptimal in one patient. Three of the four relapse cases received re-treatment with 12 weeks sofosbuvir-velpatasvir or grazoprevir-elbasvir (outside of the study protocol; SVR, n=2, lost to follow-up, n=1). There were no treatment-related serious adverse events.
Conclusions:
Glecaprevir-pibrentasvir for four weeks was safe and well tolerated among people with acute and recent HCV infection, but efficacy was lower than seen with longer treatment duration ( >= 6 weeks).