Project Grant R01AI183355

IMPILO: INVESTIGATING NOVEL 6-MONTH REGIMENS FOR RR-TB IN PREGNANCY AND LACTATION - PROJECT SUMMARY RIFAMPICIN-RESISTANT TUBERCULOSIS (RR-TB) IS A GLOBAL PUBLIC HEALTH THREAT. PREGNANT AND POSTPARTUM WOMEN ARE AT INCREASED RISK OF TB AND RR-TB, ESPECIALLY AMONG THOSE WITH HIV. MATERNAL TB INCREASES THE RISKS OF MATERNAL MORBIDITY AND MORTALITY, ADVERSE PREGNANCY OUTCOMES AND TRANSMISSION OF BOTH TB AND HIV TO THEIR INFANTS. IN 2022 THE WORLD HEALTH ORGANIZATION RECOMMENDED A NOVEL ALL-ORAL 6-MONTH REGIMEN FOR RR-TB. HOWEVER, AS VERY FEW PREGNANT WOMEN WERE INCLUDED IN THE CLINICAL TRIALS, THERE ARE LIMITED DATA ON THE USE OF THIS REGIMEN DURING PREGNANCY. ADHERENCE TO RR-TB THERAPY COULD BE REDUCED BOTH IN PREGNANCY (E.G., DUE TO NAUSEA AND VOMITING), AND IN THE POSTPARTUM PERIOD, DRIVEN BY DEPRESSION, WHICH HAS A HIGH INCIDENCE IN THE POSTPARTUM PERIOD IN OUR SETTING. DETERMINING FACTORS ASSOCIATED WITH ADHERENCE TO RR-TB TREATMENT DURING PREGNANCY AND THE POSTPARTUM PERIOD IS CRITICAL FOR DEVELOPING EVIDENCE-BASED INTERVENTIONS. IN AIM 1 OF THE PROPOSED STUDY, WE WILL ENROL PREGNANT AND NON-PREGNANT WOMEN OF CHILDBEARING POTENTIAL WITH RR-TB AND MONITOR THEIR ADHERENCE USING ELECTRONIC ADHERENCE MONITORING DEVICES. WE WILL SCREEN FOR DEPRESSION USING VALIDATED SCREENING TOOLS. WE WILL COMPARE ADHERENCE BETWEEN PREGNANT AND NON-PREGNANT WOMEN, AND ALSO COMPARE ADHERENCE DURING PREGNANCY WITH THE POSTPARTUM PERIOD. INADEQUATE TB DRUG CONCENTRATIONS ARE ASSOCIATED WITH TREATMENT FAILURE AND INCREASE THE RISK OF THE DEVELOPMENT OF RESISTANCE. THE PHYSIOLOGICAL CHANGES OF PREGNANCY DECREASE THE EXPOSURE OF MOST DRUGS AND THEREFORE, IT IS ESSENTIAL TO DETERMINE WHETHER ADEQUATE CONCENTRATIONS OF RR-TB DRUGS ARE REACHED IN PREGNANCY. IN AIM 2 OF OUR PROPOSED STUDY, WE WILL COMPARE PLASMA CONCENTRATIONS OF DRUGS IN THE NEW REGIMEN IN THE THIRD TRIMESTER WITH THE POSTPARTUM PERIOD. IF WE SHOW A MARKED REDUCTION DURING PREGNANCY OF ONE OR MORE DRUGS THIS WILL PAVE THE WAY FOR STUDIES OF DOSE ADJUSTMENT IN PREGNANCY. THERE ARE VERY LIMITED DATA DESCRIBING THE EXPOSURE OF RR-TB DRUGS IN BREASTMILK. FOR AIM 3, WE WILL DETERMINE CONCENTRATIONS OF THE DRUGS IN BREASTMILK AND INFANT PLASMA (INCLUDING SOME INFANTS WHO WILL BE BREASTFED). THESE DATA WILL INFORM RISKS ABOUT TOXICITY TO INFANTS AND POSSIBLY ALSO THE NEED FOR PREVENTIVE THERAPY. THIS STUDY PROPOSES A COMPREHENSIVE MODEL FOR INVESTIGATING NEW THERAPEUTIC INTERVENTION FOR RR-TB IN PREGNANT WOMEN WHICH INCLUDES MENTAL HEALTH, ADHERENCE, AND DRUG LEVELS. THIS WILL INFORM HOW THERAPEUTIC INTERVENTIONS FOR TB, HIV AND OTHER INFECTIOUS DISEASES IN THIS POPULATION ARE CARRIED OUT.