Background
Globally there are up to 2.3 million people living with HIV (PLHIV) and hepatitis C virus (HCV) co-infection. PLHIV with HCV co-infection are at high risk for liver-related morbidity and mortality. There are currently no approved direct acting antivirals (DAA) for acute HCV infection; however, glecaprevir/pibrentasvir (G/P) has been well studied in chronic HCV infection. Treating acute HCV could reduce onward transmission, accelerating the path to HCV elimination. The objective of this analysis was to examine the efficacy and safety of G/P in PLHIV with acute HCV, and to explore the safety of co-administration of HIV therapies with G/P.
Methods
M20-350, a phase 3b, multicenter, single-arm, open-label study, evaluated the efficacy and safety of 8-weeks of G/P for acute HCV infection in people who had not previously been treated for the current infection. Efficacy endpoints included the proportion of subjects achieving sustained virologic response 12 weeks after the last dose of G/P (SVR12) evaluated in the intention-to-treat (ITT) set (all subjects receiving ≥1 doses of G/P) and the modified ITT (mITT) set (excluding those who did not achieve SVR12 for reasons other than virologic failure). Safety endpoints included changes from baseline in alanine aminotransferase (ALT) and total bilirubin during treatment, treatment-emergent (TE) hepatic decompensation, TE serious adverse events (TESAE), and TEAE leading to G/P discontinuation. Exploratory analysis described the concomitant HIV medications taken with G/P.
Results
Of 286 subjects, 144 had acute HCV mono-infection and 142 had HIV/acute HCV infection. Table 1 provides demographics and baseline characteristics. The co-infection group SVR12 rate was 97.2% (138/142) in ITT and 100% (138/138) in mITT, with no virologic failures or virologic relapses, and one reinfection (0.7%). All PLHIV and HCV were receiving HIV medication, and 87.3% had HIV-1 RNA <20 copies/mL at baseline. No PLHIV and HCV experienced on-treatment ALT>3x ULN that worsened from baseline, hepatic decompensation, a TESAE that was deemed related to G/P, or a TEAE leading to G/P discontinuation. There were no deaths. The most common HIV treatment contained bictegravir (59/144, 41.0%). No PLHIV had two consecutive HIV-1 RNA levels ≥200 copies/mL while on G/P.
Conclusions
An 8-week treatment with G/P was safe and effective in PLHIV with acute HCV infection. Concomitant HIV antiretrovirals maintained HIV suppression and were safe to use with G/P.