Background: Hepatitis B virus (HBV) co-infection with HIV is becoming a major challenge due to shared routes of transmission. The burden is apparent in regions with widespread use of antiretroviral treatment, which led to the enhanced emergence of liver-related diseases and mortality. Though there are conflicting results about the effect of chronic HBV infection on response to highly active antiretroviral therapy (HAART) (CD4 + cell count and HIV viral load, HIV RNA copies/ml), HAART is known to cause immune mediated HBV specific liver damage after it reconstitutes cell-mediated immunity. The relationship of different HAART regimes with immune recovery is an area of research interest. Objective: It is in order to determine the changes in immune recovery during HBV infection in the setting of HAART among HIV positive individuals attending care and treatment services. Methods: Two cohorts of co-infected patients were analyzed from data of one to seven months retrospectively. The first group (n = 380) was antiretroviral drug naive and the second cohort (n = 380) was on HAART for the entire period. The study was conducted in one referral hospital and six health centers. Data were gathered from 760 patients using their intake form, their follow-up form and their medical records supplemented by data from a structured questionnaire. HBV infection was determined by using HBsAg rapid and confirmatory tests and CD4 cells were enumerated by using laboratory registers and patient cards. Bivariate and multivariate logistic regressions were done by using SPSS Version 18 and Epi info Version 3.5. Results: Poor immune recovery due to HBV infection was improved after initiation of HAART. Before the initiation of HAART, the mean CD4 cell count of HBV infected individuals was lower than that of non-HBV infected ones, 234/mm 3 and 384/mm 3 , respectively (p < 0.05). Individuals co-infected with HBV had experienced delayed recovery of immune cells (CD4 cell count). However, after, on average, more than two years of therapy, the association is reversed. In addition to HBV infection, CD4 cell count of patients on chronic HIV care/pre-ART was decreased by older age, living in rural areas and previous opportunistic infections. Conclusion: HBV infection has different outcomes between pre-ART and ART-initiated individuals. In the former cohort, HBV infection causes significant delays in immune recovery which is reversed after initiation of anti-HIV treatment. HBV co-infection has a significant and immediate negative effect on CD4 cell counts and immune recovery before HAART but such effects slowly subside after initiation of the treatment. As a result, HBV infection is another issue to consider for swift initiating of HAART for HIV infected individuals in long-term care.