Objective To investigate the long-term dynamic changes of liver function and glucose-lipid metabolism in human immunodeficiency virus (HIV)-infected patients with metabolic dysfunction-associated fatty liver disease (MAFLD) after antiretroviral therapy (ART). Methods HIV-infected patients who visited Public Health Clinical Center of Chengdu between October 1st, 2012 and June 30th, 2013 were recruited and divided into two groups according to whether they had MAFLD or not. All of them were treated with the first-line regimen of tenofovir + lamivudine + efavirenz for 156 weeks, and the anthropometric indices, liver function, and levels of glucose, lipids and uric acid were measured at baseline and at each follow-up time point. In addition, the long-term dynamic characteristics of liver function and glucose and lipid metabolism parameters of the two groups were compared during the 156 weeks of ART treatment. Results A total of 61 male HIV-infected patients were enrolled. The prevalence of MAFLD in them was 31.1% (19/61) at baseline and increased by 4.9 percentage points per year after ART. Before the start of follow-up (week 0), the levels of alanine aminotransferase (ALT) [(46.23±27.09) vs. (28.00±17.43) U/L, P=0.002] and γ-glutamyl transpeptidase (GGT) [(41.46±9.89) vs. (24.02±10.72) U/L, P<0.001] were higher in the MAFLD group than those in the non-MAFLD group, while the between-group differences in the levels of aspartate aminotransferase (AST) [(33.33±15.61) vs. (28.98±12.43) U/L, P=0.248] and alkaline phosphatase [(85.30±21.27) vs. (83.41±24.47) U/L, P=0.773] were not statistically significant. During the 156-week follow-up period, the 4 items of liver function gradually increased in the MAFLD group, especially from week 120 onwards, 3 of which (ALT, AST and GGT) were significantly higher than those in the non-MAFLD group (P<0.05). In addition, the levels of fasting blood glucose, triglyceride, total cholesterol, and low-density lipoprotein were also significantly higher in the MAFLD group than those in the non-MAFLD group at some time points during the 156-week follow-up period (P<0.05). Conclusions Compared with HIV-infected patients without MAFLD, HIV-infected patients with MAFLD are more likely to develop impaired liver function and disorders of glucose and lipid metabolism during long-term tenofovir + lamivudine + efavirenz regimen ART treatment. Therefore, close clinical monitoring of liver function and glucose and lipid metabolism related parameters is required for such patients.