Using a composite maternal-infant outcome measure in tuberculosis prevention studies among pregnant women

Background: Tuberculosis (TB) preventive therapy (TPT) among pregnant women reduces the risk of TB in mothers and infants, but the timing of initiation should consider potential adverse effects. We propose an analytical approach to evaluate the risk-benefit of interventions.

Methods: A novel outcome measure that prioritizes maternal and infant events was developed with a two-stage Delphi survey, where a panel of stakeholders assigned scores from 0 (best) to 100 (worst) based on perceived desirability. Using data from TB APPRISE, a trial among pregnant women living with HIV (WLWH) that randomized the timing of initiation of isoniazid, antepartum versus postpartum, was evaluated.

Results: The composite outcome scoring/ranking system categorized mother-infant paired outcomes into 8 groups assigned identical median scores by stakeholders. Maternal/infant TB and non-severe adverse pregnancy outcome were assigned similar scores. The mean (SD) composite outcome scores were 43.7 (33.0) and 41.2 (33.7) in the antepartum and postpartum TPT initiation arms, respectively. However, a modifying effect of baseline antiretroviral regimen was detected (p=0.049). When women received nevirapine composite scores were higher (worse outcomes) in the antepartum versus postpartum arms (adjusted difference=14.3; 95% CI: 2.4 - 26.2; p=0.02), whereas when women received efavirenz there was no difference by timing of TPT (adjusted difference=0.62; 95%CI: -3.2 to 6.2; p=0.53).

Conclusions: For TPT, when used by otherwise healthy persons, preventing adverse events is paramount from the perspective of stakeholders. Among pregnant WLWH in high TB burden regions, it is important to consider the antepartum antiretroviral regimen taken when deciding when to initiate TPT.