Objective: To evaluate the influence of hepatitis B virus (HBV) co-infection on immunological, virological and clinical responses to lamivudine-based combined antiretroviral therapy (cART) in Chinese patients. Design and methods: This prospective, multicenter cohort study recruited 529 antiretroviral-naive participants (aged 18-65 years, both genders) between 2008 and 2010. They were grouped by HBV serostatus. Virological and immunological responses were monitored at baseline and week 4, 8, 12, 24, 36 and 48. cART for all patients was nevirapine, lamivudine with either zidovudine or stavudine. Results: (1)HIV/HBV co-infection rate in our cohort was 14.6%. (2)Among 508 patients with complete baseline information, median CD4 level was significantly lower in chronic HBV-infected (CHB) group and isolated-core group. In CHB group, HBeAg positivity rather than HBV DNA level was associated with lower CD4 count. (3)In isolated-core group, occult infection rate was 9.5%. (4)At week 48, rate of HIV suppression below 40 copies/mL was 74.2%. Median increase in CD4 at week 48 was 127cells/[mu]L. Of note, HBV serostatus did not influence virological and immunological response to cART at each follow-up time point. Although HBV serostatus was associated with different ALT level during follow-up, hepatitis and hyperbilirubinemia rates were not significantly different. (5)3TC-based regimen was efficacious against HBV replication, with median decrease of HBV DNA 2.87 log copies/mL. However, HBeAg positivity was associated with poorer HBV DNA suppression. Conclusion: In our cohort, chronic HBV infection and isolated HBcAb positivity were related to faster HIV progression. Despite of this, virological and immunological responses were not affected by HBV serostatus.