BACKGROUND: The safety and efficacy of nevirapine (NVP) and efavirenz (EFV) based highly active antiretroviral treatment (ART) with concurrent anti-tuberculosis treatment in sub-Saharan Africa has not been well established. METHODS: We performed a retrospective study comparing human immunodeficiency virus (HIV) infected adults exposed and not exposed to tuberculosis (TB) treatment with similar baseline HIV-1 RNA levels who were started on ART as part of Botswana's ART Programme. ART regimens, HIV-1 RNA, CD4+ cell count, and liver function tests were reviewed for 12 months following ART initiation. RESULTS: Among 155 patients on ART only and 155 exposed to TB treatment, there was no difference in virologic or immunologic response throughout the first year of ART. Furthermore, there remained no differences in virologic or immunologic outcomes when NVP and EFV groups were stratified by TB treatment exposure status. While more hepatotoxic events occurred in the group exposed to TB treatment than in those not exposed (9% vs. 3%, P = 0.05), there was no difference between patients treated with NVP and those treated with EFV. CONCLUSIONS: Patients co-infected with HIV and TB in Botswana can be treated effectively with either NVP- or EFV-based ART and TB treatment. As hepatotoxic events were more common in the group exposed to TB treatment, liver function tests should be monitored closely.