Maraviroc with or Without Metformin for the Treatment of Non-Alcoholic Fatty Liver Disease in Virologically Suppressed Adults with HIV (MAVMET)
Neither maraviroc nor metformin significantly reduced liver fat percentage in adults with HIV and NAFLD compared to standard antiretroviral therapy.
Where it sits
this study against the rest of the tesamorelin corpusSummary and findings
This study evaluated the effects of maraviroc and metformin on liver fat percentage in virologically suppressed adults with HIV and non-alcoholic fatty liver disease (NAFLD). A total of 90 participants were enrolled and followed for 48 weeks. The primary outcome showed no significant reduction in liver fat percentage compared to antiretroviral therapy alone.
Abstract
Background: Non-alcoholic fatty liver disease (NAFLD), a manifestation of metabolic syndrome, is over-represented in people living with HIV (PLWH). Maraviroc, a C-C chemokine receptor type-5 (CCR5) inhibitor, and metformin, a biguanide anti-glycaemic, may reduce hepatic steatosis/steatohepatitis through their influence on inflammatory pathways (metformin & maraviroc), and free fatty acid metabolism (metabolism).<br><br>Methods: MAVMET (NCT#:03129113), is a multi-centre, open-label, 48-week randomised trial with a 2x2 factorial design of adjunctive maraviroc (MVC); metformin (MET); maraviroc+metformin (MVC+MET) vs. antiretroviral therapy (ART) alone in non-diabetic, virologically-suppressed PLWH, aged ≥35 years, with confirmed/suspected NAFLD (≥1 biochemical/anthropometric/radiological/ histological feature suggestive of/confirming hepatic steatosis). The primary outcome was change in liver fat percentage between baseline and week 48, using the Magnetic Resonance Proton Density Fat Fraction (MR PDFF), analysed using linear regression, and adjusted for COVID-19-related delays in week-48 scans.<br><br>Findings: 90 participants [93% male; 81% white ethnicity; median age 52 (IQR 47-57) years], were enrolled between 19-Mar-2018 and 11-November-2019 from six UK sites; 70% with imaging/biopsy plus ≥1 criteria for NAFLD. The primary analysis included 82/90 with both week 0 and 48 scans. Mean (Standard deviation, SD) baseline PDFF was 11.8% (8.7); 40%, 38%, 8% and 14% had grade 0,1, 2 and 3 hepatic steatosis respectively. Mean PDFF (SD) at week 48 was 12.9% (9.0). Hepatic steatosis grade remained unchanged in 55% and increased in 24% (n=20). Remaining on study drugs for longer (delayed week-48 scans) was associated with greater increases in liver fat percentage. The small decreases (absolute and relative to ART alone) in liver fat percentage with MVC or MET [MVC -0.42% (95% CI -1.53-0.68, p=0.45), MET -0.62 (-1.81-0.56, p=0.30), MVC+MET -1.04 (-2.74-0.65, p=0.23)] were non-significant.<br><br>Interpretation: Baseline levels of liver fat were lower than predicted. Contrary to our hypothesis, neither MVC, MET or the combination, significantly reduced the LFF compared to ART alone.<br><br>Trial Registration: MAVMET was registered at ClinicalTrials.gov (NCT#: 03129113) and with EudraCt (2016- 163 003575-21). <br><br>Funding: ViiV Healthcare, UK funded the study as an independent academic grant (ViiV Reference Etrack Number 204817).<br><br>Declaration of Interest: We declare no competing interests.<br><br>Ethical Approval: Ethical approval was authorised by the London-Hampstead Research Ethics Committee 161 (17/LO/0998). MAVMET was granted Clinical Trial Authorisation (CTA# 00316/0247/001- 162 0001). All participants provided written informed consent prior to study procedures.