Study background: Poor CD4 T-lymphocyte responses to anti-retroviral treatment (ART) are associated with increased HIV disease progression and mortality. In sub-Saharan Africa a substantial proportion of HIV infected patients are co-infected with TB. This study evaluated the effect of active TB presenting after ART initiation on immunological responses to ART. Methods: A retrospective cohort study was conducted of patients initiated on ART in a South African academic hospital between 1 January 2004 and 15 May 2008. Changes in CD4 T-lymphocyte count, virological suppression and incident TB episodes occurring in the fi rst year of ART were assessed. Sub-optimal CD4 responses were defi ned as ‘failure to increase CD4 T-lymphocyte count by 50cells/µl at 6 month on ART’. Results: The cohort for analysis included 691 patients. 141 (20.4%) had sub-optimal CD4 responses at 6 months on ART. 49 patients (7.1%) developed incident TB within the fi rst 12 months of ART. After adjustment for age, sex, baseline CD4 count and detectable viral load, patients with incident TB were found to have a 2.20 times greater odds of a sub-optimal CD4 response at 6 month of ART as compared to those who were TB free (95%CI: 1.14-4.23). Conclusion: Incident TB was associated with a poor CD4 response during early ART in this cohort. Although the direction of causality cannot be determined from these data, these fi ndings provide additional support for the initiation of ART at higher CD4 counts