Background Hepatitis B virus (HBV) co-infection in human immunodeficiency virus (HIV)-positive individuals increases the risk of overall mortality, especially when HBV DNA levels are high. The role of CD4 + cell counts in this association is poorly defined. We aimed to determine whether HIV\textendash HBV co-infection influences changes in CD4 + cell count before and during antiretroviral therapy and whether it affects mortality risk at levels of CD4 + . Methods 2052 HIV-positive participants from Côte d'Ivoire in a randomized-control trial assessing early or deferred ART were included. HBV-status was determined by hepatitis B surface antigen (HBsAg). Changes in CD4 + cell levels were estimated using a mixed-effect linear model. The incidence rates of all-cause mortality were estimated at CD4 + counts ≤q350, 351\textendash 500, >500/mm 3 and were compared between HBV-status groups as incidence rate ratios (IRR). Results At baseline, 190 (9%) were HBsAg-positive [135 (71%) with HBV DNA 500/mm 3 (adjusted-IRR = 1.07, 95% CI = 0.01\textendash 4.91). Conclusion Despite no effect of HBV-infection on CD4 + levels, HIV-HBV co-infected individuals with high HBV replication are at higher risk of mortality when CD4 + is <500/mm 3 .Read less <