We examined the effect of combination antiretroviral therapy (cART) on liver fibrosis among HIV-infected patients with or without hepatitis B (HBV) or C virus (HCV) co-infection. This was a retrospective cohort study of HIV-infected patients receiving cART during 2004-2016. Liver fibrosis was assessed using Fibrosis-4 (FIB-4) score with three classifications: Class 1,3.25. Of 3900 participants, 68.6% were HIV mono-infected, 5.3% were HIV/HBV co-infected, 23.8% were HIV/HCV co-infected and 2.3% were HIV/HBV/HCV co-infected. Participants received follow-up treatment (median was 3.3 years). Improvement to a lower class was observed in Class 2 (52.6%) and Class 3 (74.2%), respectively. Progression to a higher class was observed in 12.8% and 5.0% in Class 1 and Class 2, respectively, and with a median time of 5.7 months. For improvement to lower classes, older age, male, Dai ethnicity, injection drug use, HCV co-infection and tenofovir for treatment were negative predictors, but in Class 3 of FIB-4 and time-updated increases in CD4 count from baseline were positive predictors. For progression to higher classes, older age, male, Jingpo ethnicity and HCV co-infection were positive predictors, while baseline CD4 count and in Class 2 of FIB-4 were negative predictors. Improvement to lower class linked with decreased mortality risk among patients in Class 3. Early cART initiation for HIV-infected patients with and without hepatitis co-infections may mitigate or slow down some of liver fibrosis, but special attention should be given to those who are older, male, co-infected with HCV.