Tuberculosis Preventive Treatment for Pregnant People With Human Immunodeficiency Virus in South Africa: A Modeling Analysis of Clinical Benefits and Risks

Background: Although prior studies of tuberculosis-preventive treatment (TPT) for pregnant people with human immunodeficiency virus (PPWH) report conflicting adverse pregnancy outcome (APO) risks, international guidelines recommend TPT for PPWH. Methods: We used a microsimulation model to evaluate 5 TPT strategies among PPWH receiving antiretroviral therapy in South Africa: No TPT; 6 months of isoniazid (6H) or 3 months of isoniazid-rifapentine (3HP) during pregnancy (Immediate 6H or Immediate 3HP) or post partum (Deferred 6H or Deferred 3HP). The primary outcomes were maternal, fetal/infant, and combined deaths from causes potentially influenced by TPT (maternal tuberculosis, maternal hepatotoxicity, stillbirth, low birth weight [LBW], and infant tuberculosis). Tuberculosis during pregnancy confers 250% and 81% higher modeled risks of stillbirth and LBW, respectively. In lower-risk or higher-risk scenarios, immediate TPT confers 38% lower or 92% higher risks of stillbirth and 16% lower or 35% higher risks of LBW. Results: Immediate TPT would minimize deaths among PPWH. When TPT confers higher stillbirth and LBW risks, immediate TPT would produce the most combined maternal and fetal/infant deaths, even with low maternal CD4 cell count and high tuberculosis incidence. If immediate TPT yields a <4% or <20% increase in stillbirth or LBW, immediate TPT would produce fewer combined deaths than deferred TPT (sensitivity analysis range, <2%-22% and <11%-120%, respectively). Conclusions: If APO risks are below identifiable thresholds, TPT during pregnancy could decrease combined maternal and fetal/infant deaths. Given uncertainty around isoniazid's risks, and the low threshold at which APO risks could outweigh benefits from tuberculosis deaths averted, studies of newer TPT regimens among PPWH are warranted to inform guidelines.