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Six-Week SOF/VEL Inferior to 12 Weeks for Recently Acquired HCV
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CROI 2020, March 8-11, 2020, Boston
Mark Mascolini
HCV relapse proved significantly more frequent with 6 versus 12 weeks of sofosbuvir/velpatasvir (SOF/VEL) for recently acquired HCV infection [1]. Sustained virologic response 12 weeks after treatment stopped (SVR12) measured 82% with 6-week SOF/VEL and 91% with 12 weeks in this international randomized trial, the REACT study.
No direct-acting antiviral (DAA) regimens are approved for acute HCV infection, and current guidelines take a conservative stance on treating acute infection. REACT aimed to compare 6-week and 12-week SOF/VEL therapy in people who inject drugs and people with HIV coinfection who have acute or recently acquired HCV [2].
The trial enrolled people at 24 sites in 8 countries. The primary analysis involved 192 participants, 93 randomized to 6-week therapy and 99 to 12 weeks. Most people in both arms were men (96% overall) and had HIV infection (69%), while 21% injected drugs. Median age stood at 43 years. While 63% had primary HCV infection, 37% had reinfection. Estimated HCV infection duration at baseline stood at a median 25 weeks (range 7 to 60).
At study week 24, proportions with SVR12 in an intention-to-treat (ITT) analysis including all randomized participants were 82% with 6 weeks of SOF/VEL and 91% with 12 weeks, a difference that stopped just short of statistical significance (difference -9.2%, confidence interval -18.9% to 0.5%, P = 0.063). In a modified ITT analysis, SVR12 rates were 89% with 6 weeks of SOF/VEL and 98% with 12 weeks, a significant difference (difference -8.8%, confidence interval -15.6% to -1.2%, P = 0.021). This analysis excluded nonvirologic reasons for treatment failure: loss to follow-up (5), death (2), and confirmed reinfection (5).
Researchers counted 9 virologic relapses with 6 weeks of therapy and 2 relapses with 12 weeks. Relapse occurred at a median HCV load of 6.7 log after a median 28 weeks in participants with a median age of 50 years. New resistance emerged in only 1 of 11 people with relapse, a person in the 6-week group.
There were 11 serious adverse events, only 1 of them treatment-related. No one stopped therapy for treatment-related reasons.
REACT investigators deemed the relapse rate unacceptably high in the 6-week SOF/VEL arm. But they found good engagement and adherence rates, with only 1 treatment discontinuation, only 5% lost to follow-up, and 93% of participants with greater than 90% adherence. Despite the high relapse rate in the 6-week arm, they rated overall treatment successful and safe, "supporting the feasibility and importance of treating early."
References
1. Matthews GV, Bhagani S, Van der Valk M, et al. Inferiority of short duration sofosbuvir-velpatasvir for recent HCV (REACT Study). Conference on Retroviruses and Opportunistic Infections (CROI). March 8-11, 2020. Boston. Abstract 121.
2. ClinicalTrials.gov. Randomised Study of Interferon-free Treatment for Recently Acquired Hepatitis C in PWID and People With HIV Coinfection. (REACT). ClinicalTrials.gov Identifier: NCT02625909.
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“all patients with viral failure were successfully retreated the majority with first-line regimens. Patient #1 see table below, had no baseline resistance but L31M in followup & was successfully retreated with Sofosbuvir/Velpatasvir/Voxilaprevir”.
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