TB-HAART study is a randomized, placebo-controlled trial performed between 2008 and 2013 at 26 sites in South Africa, Tanzania, Uganda and Zambia. 1,675 HIV positive patients with culture-confirmed tuberculosis who had tolerated 2 weeks of tuberculosis chemotherapy were randomized to early ART (starting after 2 weeks of tuberculosis treatment, n= 834) or delayed ART (placebo then starting ART at the end of 6 months of tuberculosis treatment, n= 841). ART was ZDV/3TC bid + EFV qd. Randomization was stratified by CD4 count (220–349 cells per μL vs ≥ 350 cells per μL). Following the 6 months tuberculosis treatment of double-blind follow-up, the study was open-label. The primary endpoint was a composite of failure of tuberculosis treatment, tuberculosis recurrence, and death within 12 months of starting tuberculosis treatment in the modified intention-to-treat population. The proportion of patients achieving the primary endpoint was similar in both groups: 8.5% in the early ART group versus 9.2% in the delayed ART group (relative risk 0.91, 95% CI: 0.64–1.30; p= 0.9). There was no difference in outcome in the two CD4 sub-groups: for patients with CD4 cell count of 220-349 cells per μL ,7.9% versus 9.6% reached the primary endpoint (relative risk 0.80, 95% CI: 0.46–1.39; p= 0.6); for patients with CD4 ≥ 350 cells per μL, 8.9% versus 8.9% reached the primary endpoint (relative risk 1.01, 95% CI: 0.63–1.62; p= 0.4). Mortality did not differ significantly between treatment groups (relative risk 1.4, 95% CI: 0.8–2.3; p= 0.23). Grade 3 and 4 adverse events occurred in 18% to the early ART group versus 21% in the delayed ART group (p= 0.37), and immune reconstitution syndrome occurred in 10% versus 10% (p= 0.56).

In conclusion, ART can be delayed until after completion of 6 months of tuberculosis treatment for HIV positive patients with tuberculosis who have CD4 cell counts greater than 220 cells per μL. WHO guidelines should be updated accordingly .