Effect of highly active antiretroviral therapy on incidence of tuberculosis in South Africa: a cohort study

Background Studies of the effect of highly active antiretroviral therapy (HAART) on the risk of HIV-1-associated tuberculosis have had variable results. We set out to determine the effect of HAART on the risk of tuberculosis in South Africa. Methods We compared the risk of tuberculosis in 264 patients who received HAART in phase III clinical trials and a prospective cohort of 770 non-HAART patients who were attending Somerset Hospital adult HIV clinic, University of Cape Town, between 1992 and 2001. Poisson regression models were fitted to determine risk of tuberculosis; patients were stratified by CD4 count, WHO clinical stage, and socioeconomic status. Findings HAART was associated with a lower incidence of tuberculosis (2•4 vs 9•7 cases per 100 patient-years, adjusted rate ratio 0•19 [95% CI 0•09–0•38]; p<0•0001). This finding was apparent across all strata of socioeconomic status, baseline WHO stage, and CD4 count, except in patients with CD4 counts of more than 350 cells/μL. The number of tuberculosis cases averted by HAART was greatest in patients with WHO stage 3 or 4 (18•8 averted cases per 100 patient-years, adjusted rate ratio 0•22 [0•09–0•41]; p=0•03) and in those with CD4 counts of less than 200 cells/μL (14•2 averted cases per 100 patient-years, adjusted rate ratio 0•18 [0•07–0•47]; p<0•0001). Interpretation HAART reduced the incidence of HIV-1-associated tuberculosis by more than 80% (95% CI 62–91) in an area endemic with tuberculosis and HIV-1. The protective effect of HAART was greatest in symptomatic patients and those with advanced immune suppression.