Setting: International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1041, a tuberculosis (TB) prevention trial conducted among children enrolled from 2004 to 2008 during South Africa's roll-out of combination antiretroviral therapy (ART).
Objective: To estimate TB incidence and mortality and the effect of ART.
Design: Children were pre-screened to exclude TB disease and exposure, actively screened 3-monthly for TB exposure and symptoms, and provided post-exposure isoniazid prophylaxis therapy (IPT). TB diagnoses were definite, probable, or possible, and mortality all-cause. Testing was at the 5% significance level.
Results: In 539 children (aged 3-4 months) followed up for a median of 74 weeks (interquartile range [IQR] 48-116), incidence/100 person-years (py) was 10.67 (95%CI 8.47-13.26) for any TB and 2.89 (95%CI 1.85-4.31) for definite/probable TB. Any TB incidence was respectively 9.39, 13.59, and 9.83/100 py before, <180 days after, and 180 days after ART initiation. Adjusted analysis showed a non-significant increase in any TB (HR 1.32, 95%CI 0.71-2.52, P = 0.38) and a significant reduction in mortality (HR 0.39, 95%CI 0.17-0.82, P = 0.017) following ART initiation.
Conclusions: ART reduced mortality but not TB incidence in human immunodeficiency virus (HIV) infected children in IMPAACT P1041, possibly attributable to active screening for TB exposure and symptoms with post-exposure IPT. Research into this as a strategy for TB prevention in high HIV-TB burden settings may be warranted.