Individual and Composite Adverse Pregnancy Outcomes in a Randomized Trial on Isoniazid Preventative Therapy Among Women Living With HIV

Background: IMPAACT P1078, a randomized non-inferiority study designed to compare safety of starting isoniazid preventive therapy (IPT) in women with HIV during pregnancy or after delivery, showed that IPT during pregnancy increased the risk of composite adverse pregnancy outcomes, but not individual outcomes. Many known factors are associated with adverse pregnancy outcomes, their association and effect modification with IPT and pregnancy outcomes were examined.

Methods: HIV-infected pregnant women from 8 countries with TB incidence >60/100,000, were randomly assigned to initiate 28 weeks of IPT either during pregnancy or at 12 weeks after delivery. Using univariable and multivariable logistic regression adjusting for factors associated with pregnancy outcomes, composite and individual adverse pregnancy outcome measures were analyzed.

Results: This secondary analysis included 925 mother-infant pairs. All mothers were receiving antiretrovirals. The adjusted odds of fetal demise, preterm delivery (PTD), low birth weight (LBW) or congenital anomaly (composite outcome 1) were 1.63 times higher among women on immediate compared to deferred IPT (95% CI=1.15, 2.31). The odds of fetal demise, PTD, LBW or neonatal death within 28 days (composite outcome 2) were 1.62 times higher among women on immediate IPT (95% CI=1.14, 2.30). The odds of early neonatal death within 7 days, fetal demise, PTD, or LBW (composite outcome 3) were 1.74 times higher among women on immediate IPT (95% CI=1.22, 2.49).

Conclusions: We confirmed higher risks of adverse pregnancy outcomes associated with initiation of IPT during pregnancy after adjusting for known risk factors for adverse pregnancy outcomes.