MAVMET trial: maraviroc and/or metformin for metabolic dysfunction-associated fatty liver disease(MAFLD) in adults with suppressed HIV.
Mccabe L., Burns JE., Latifoltojar A., Post FA., Fox J., Pool E., Waters A., Santana B., Garvey L., Johnson M., Mcguinness I., Chouhan M., Edwards J., Goodman AL., Cooke G., Murphy C., Collaco-Moraes Y., Webb H., Gregory A., Mohamed F., Rauchenberger M., Ryder SD., Sandford C., Baker JV., Angus B., Boesecke C., Orkin C., Punwani S., Clark A., Gilson R., Dunn D., Pett SL., MAVMET Study group None.
ObjectiveMetabolic dysfunction-associated fatty liver disease (MAFLD) is over-represented in people living with HIV (PLWH). Maraviroc (MVC) and/or metformin (MET) may reduce MAFLD by influencing inflammatory pathways and fatty acid metabolism.DesignOpen-label, 48-week randomised trial with a 2x2 factorial design.SettingMulticentre HIV clinics.ParticipantsNondiabetic, virologically-suppressed PLWH, aged ≥35 years, with confirmed/suspected MAFLD (≥1 biochemical/anthropometric/radiological/histological features).InterventionAdjunctive MVC; MET; MVC+MET vs. antiretroviral therapy (ART) alone.Primary outcomeChange in liver fat fraction (LFF) between baseline and week-48 using Magnetic Resonance Proton Density Fat Fraction (MR PDFF).ResultsSix sites enrolled 90 participants (93% male; 81% white; median age 52 [interquartile range, IQR 47-57] years) between 19-Mar-2018 and 11-November-2019. 70% had imaging/biopsy plus ≥1 MAFLD criteria. The analysis included 82/90 with week-0 and -48 scans. Median baseline MR PDFF was 8.9 (4.6-17.1); 40%, 38%, 8%, and 14% had grade zero, one, two, and three steatosis respectively. Mean LFF increased slightly between baseline and follow-up scans: 2.22% MVC, 1.26% MET, 0.81% MVC+MET, and 1.39% ART alone. Prolonged intervention exposure (delayed week-48 scans) exhibited greater increases in MR PDFF (estimated difference 4.23% [95% CI 2.97, 5.48], P ConclusionsBaseline levels of liver fat were lower than predicted. Contrary to our hypothesis, neither MVC, MET, or the combination significantly reduced MR PDFF compared to ART alone.