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 < 0.001). There were no differences in predicted change for any intervention compared to ART alone: MVC (-0.42% [95% CI -1.53-0.68, P = 0.45]), MET (-0.62 [-1.81-0.56, P = 0.30]), and MVC+MET (-1.04 [-2.74-0.65, P = 0.23]). Steatosis grade remained unchanged in 55% and increased in 24%.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.