Early versus delayed initiation of highly active antiretroviral therapy for HIV-positive adults with newly diagnosed pulmonary tuberculosis (TB-HAART): a prospective, international, randomised, placebo-controlled trial.
Mfinanga SG, Kirenga BJ, Chanda DM, Mutayoba B, Mthiyane T, Yimer G, Ezechi O, Connolly C, Kapotwe V, Muwonge C, Massaga J, Sinkala E, Kohi W, Lyantumba L, Nyakoojo G, Luwaga H, Doulla B, Mzyece J, Kapata N, Vahedi M, Mwaba P, Egwaga S, Adatu F, Pym A, Joloba M, Rustomjee R, Zumla A, Onyebujoh P.
Lancet Infect Dis. 2014 Jul;14(7):563-71.
13 February 2015, by Dr Anton Pozniak
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 .
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