Isoniazid monotherapy for tuberculosis prevention during pregnancy and adverse outcomes in women living with HIV in Uganda: A propensity score-weighted analysis of routine care data.

Data on the safety of tuberculosis preventive treatment (TPT) during pregnancy particularly from routine care settings in high tuberculosis (TB) burden countries remain limited. We evaluated the association between TPT exposure during pregnancy and adverse pregnancy outcomes among pregnant women living with HIV (WLHIV) in Uganda. We conducted a retrospective cohort study using routinely collected data from five public urban primary health facilities in Kampala, Uganda. We included pregnant women living with HIV on antiretroviral therapy (ART) between 2016 and 2022. The primary outcome was a composite of adverse pregnancy outcomes: miscarriage, stillbirth, low birth weight, neonatal complications, or maternal/neonatal death. A secondary composite outcome excluded neonatal and maternal death. There was no preterm delivery documented in this sample. The primary exposure was 6-month isoniazid preventive therapy (IPT) during pregnancy. We applied inverse probability of treatment weighting (IPTW) using propensity scores from logistic regression to adjust for confounding. Missing data on covariates and outcome were addressed using multiple imputation. Analysis was performed using R software v.4.3.3. We analyzed data from 521 pregnant WLHIV, the median age was 28 years (interquartile range 24-31), 44% of whom received IPT during pregnancy. Overall, 10.0% experienced an adverse pregnancy outcome. No significant differences were observed between IPT-exposed and unexposed groups for the primary (10.3% vs. 9.6%; p = 0.81) or secondary (10.3% vs. 8.5%; p = 0.50) composite outcomes. IPTW-adjusted analysis showed no significant association between IPT exposure and adverse pregnancy outcomes (weighted OR: 1.06; 95% CI: 0.68-1.63; p = 0.81). Sensitivity and subgroup analyses yielded consistent findings. Exposure to 6-month isoniazid TPT during pregnancy was not statistically associated with adverse pregnancy outcomes among women on ART in routine care settings. Strengthened pharmacovigilance and systematic clinical reporting are essential to ensure maternal and neonatal safety as TPT coverage expands in high TB/HIV burden settings.