Rifapentine in High Doses in Pregnancy with TB (Radiant-Moms) study

SUMMARY The risk of tuberculosis (TB) is twice as high during and immediately after pregnancy than any other time in a person’s life, and pregnant people with TB who are co-infected with HIV are at higher risk for mortality. More than 200,000 pregnant people develop TB annually, with the majority living in Africa, where HIV prevalence is high, and Asia. Pregnancy carries a high risk of adverse outcomes including miscarriage, preterm birth and increased risk of maternal to child HIV transmission. Thus, optimizing care for pregnant and breastfeeding people (PBP) should be a global priority. However, PBP are routinely excluded from TB clinical trials and denied equal access to novel TB treatment options. In 2013, a panel of experts published a consensus statement for accelerated inclusion of PBP in TB clinical trials. A new shorter TB treatment regimen is now recommended as an option for adults and adolescents globally; but not PBP. Potential access to this regimen will remain limited in PBP without the required data regarding dosing and safety for PBP and the developing fetus. There is a perception that the standard regimen is sufficient and safe, and that PBP would not want to take a new regimen. However, no one has asked PBP, TB program managers or healthcare providers (HCP) in TB-endemic countries what guides their decisions to take or recommend treatment regimens in PBP. The Radiant-Moms study will use discrete choice experiment (DCE) to examine preferences among PBP and HCP regarding novel shorter TB treatment regimens during the pregnancy and postpartum periods. We will conduct the study in South Africa and the Philippines, representing different geographical settings with high TB burden and varying HIV prevalence. We will employ a two-phase mixed-methods design. In Phase I we will use qualitative methods to elicit input from stakeholders from the target populations: PBP, HCP, key informants, and community influencers from each country to determine optimal DCE survey design. We will also conduct in-depth qualitative cohort interviews in PBP with recent TB over time to gain an in-depth understanding of experiences during pregnancy and the postpartum period. In Phase II, quantitative activities will consist of a structured survey among PBP and HCP, including preferences for attributes of TB treatment regimens and service delivery models (DCE). We will also identify barriers and facilitators to inclusion of PBP in TB trials among key stakeholders. Radiant-Moms will generate key evidence to support the evaluation, adoption, and safe practical implementation of new shorter TB treatment regimens during pregnancy and postpartum programmatically and provide global impetus and guidelines for their broader use with substantial benefits that shorter effective treatment may confer to PBP and their infants. Data from this study will help inform prioritization and implementation of future trials including safety and pharmacokinetic studies of new TB regimens in pregnancy and the postpartum period. Radiant-Moms will provide a model for the earlier and appropriate inclusion of PBP in clinical trials of novel TB treatments, for drug-susceptible and drug-resistant TB and prevention in the future.