Impact of an add-on strategy of the C-C chemokine receptor 5 (CCR5) antagonist maraviroc on hepatic inflammation in HIV-infected individuals with non-alcoholic steatohepatitis: a paired-liver biopsy proof-of-concept study

Abstract

Introduction. Non-alcoholic steatohepatitis (NASH) is of concern in an aging and antiretroviral therapy (ART)-pretreated HIV-infected population. No therapeutic agent has yet been licensed for the treatment of NASH in order to reduce hepatic inflammation, steatosis, or liver fibrosis. The CCR5 receptor antagonist maraviroc is an approved HIV drug, but hepatic CCR5 inhibition has also been suggested to reduce hepatic inflammation and fibrogenesis in animal models. This study aimed to investigate the impact of a maraviroc add-on strategy on hepatic inflammation in ART-treated HIVmono-infected individuals with NASH. Methods. The MASH study (Maraviroc-Add on for Steatohepatitis in HIV infected patients) was a single-arm, open-label trial conducted across 5 sites in Germany and the United Kingdom. HIV-infected individuals with biopsy proven NASH were invited to add maraviroc BID to their existing, suppressive ART regimen for 48 weeks, and undergo a second liver biopsy thereafter. Patients had immunologic, cytokine, metabolic, and histologic assessment at baseline and end of treatment (EOT). Results. Overall, 24 subjects were screened, and 13 completed the study and were analyzed. All participants were male, median age 50.5 years [45.5-55.5], baseline BMI 30.66 kg/m2 [27.92-33.63]; 83.3% (10/12) had insulin resistance. At baseline, 11/13 patients (85%) had fibrosis >1 (Metavir). At EOT no significant changes in the hepatic immune cell infiltrate (CD4/CD8/CD68) were observed, however, the NAS score decreased non significantly from 4.077 ± 0.76 at baseline to 3.64 ± 0.51 at EOT (p = 0.125). At week 48, 7/11 patients (63%) showed significant fibrosis> stage 1, EOT BMI was similar compared to baseline. Add-on MVC had no significant impact on inflammatory markers or lipid metabolism.