Introduction: Since the initiation of regular antiretroviral therapy and highly active antiretroviral therapy (HAART) in South Africa in 2004, data on effects of HAART on mortality are not available in our hospital.

Objectives: We sought to describe mortality trends and causes of deaths among HIV‑infected patients in the HAART era.

Patients and methods: Consecutive HIV‑infected adults who were prescribed HAART in our hospital were prospectively followed‑up from July 2004 to December 2006 or until death, loss to follow‑up, discontinuation of HAART or referral to another center.

Results: Out of 2605 HIV‑infected patients analyzed at the end of 2006, 7.8% (n = 205) died. The causes of these 205 deaths were dominated by AIDS related disorders such as opportunistic infection (47.6%) and advanced AIDS status (37.3%). Non‑AIDS infectious diseases, liver diseases, cardiovascular diseases, and cancers were rare. Mortality rate was higher in males (28%, p <0.0001) than females (8%) as well as in subgroup with CD4 cell counts <200/μl (8%, p <0.0001) than in subgroup with CD4 cell counts >200/μl (4.9%). There was a negative significant dose – response relationship (p for linear trend <0.0001) between mortality and baseline CD4 cell counts among patients with CD4 cell counts <200/μl, 13% in the CD4 <50/μl group, 6% in the CD4 51–100/μl group, 5.5% in the CD4 101–150/μl group, and 3% in the CD4 >151/μl group. Mortality was not associated with age and HAART regimens.

Conclusions: Prevention of AIDS‑defining conditions and expansion of earlier access to HAART could substantially reduce mortality in resource‑poor settings.