No advantage with early ART in TB patients with CD4 count above 220
Starting antiretroviral therapy (ART) 2 weeks after TB therapy began did not lower proportions of African patients who reached a composite endpoint including TB treatment failure, TB recurrence, and death, according to results of a randomized double-blind trial in people with a CD4 count above 220 cells/µL. The findings contrast with two earlier trials in which starting ART early in the course of TB therapy had marked clinical benefits in people with a CD4 count below 50 or 200 cells/µL.
The two earlier trials took place in South Africa (SAPiT) and Cambodia (CAMELIA) (click on links below). SAPiT found that, among people with an initial CD4 count below 50 cells/µL, those who started ART earlier had almost a 70% lower incidence of AIDS or death than people who started ART later, though that difference stopped just short of statistical significance (incidence rate ratio 0.32, 95% confidence interval [CI] 0.07 to 1.13, P = 0.06). In HIV/TB-coinfected people with a CD4 count below 200 cells/µL, CAMELIA found that early ART lowered the risk of death almost 40%, a significant difference (hazard ratio 0.62, 95% CI 0.44 to 0.86, P = 0.006).
The World Health Organization (WHO) recommends early ART for all HIV/TB-coinfected people, regardless of CD4 count. To further assess the value of early ART in people with a CD4 count above 220 cells/µL, the new trial (TB-HAART) in South Africa, Tanzania, Uganda, and Zambia enrolled 1675 people who had tolerated 2 weeks of short-course TB therapy and randomized them to early ART (after 2 weeks of TB therapy) or delayed ART (placebo then ART after 6 months of TB treatment).
Neither patients nor physicians knew which participants were taking active antiretrovirals or placebo. The composite primary endpoint included TB treatment failure, TB recurrence, and death within 12 months of starting TB therapy in a modified intention-to-treat analysis.
Sixty-five people in the early-ART group (8.5%) and 71 (9.2%) in the delayed-ART group reached the primary endpoint, a nonsignificant difference (relative risk 0.91, 95% CI 0.64 to 1.30, P = 0.9). Proportions of participants reaching the primary endpoint did not differ significantly when the researchers limited the analysis to people with an initial CD4 count between 220 and 349 cells/µL or to participants with a CD4 count of 350 cells/µL or more. Nor did mortality alone differ significantly between the two treatment groups.
Grade 3 or 4 adverse events arose in 18% in the early-ART group and 21% in the delayed-ART group, a nonsignificant difference. Immune reconstitution inflammatory syndrome (IRIS) developed 10% in each treatment group.
The TB-HAART researchers conclude that “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.” They propose that “WHO guidelines should be updated accordingly.”
Source: Sayoki G Mfinanga, Bruce J Kirenga, Duncan M Chanda, Beatrice Mutayoba, Thuli Mthiyane, Getnet Yimer, Oliver Ezechi, Cathy Connolly, Vincent Kapotwe, Catherine Muwonge, Julius Massaga, Edford Sinkala, Wanze Kohi, Lucinda Lyantumba, Grace Nyakoojo, Henry Luwaga, Basra Doulla, Judith Mzyece, Nathan Kapata, Mahnaz Vahedi, Peter Mwaba, Saidi Egwaga, Francis Adatu, Alex Pym, Moses Joloba, Roxana Rustomjee, Alimuddin Zumla, Philip Onyebujoh. 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. Lancet Infectious Diseases. Available online 5 May 2014
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Source: IAS
