DESCRIPTION (provided by applicant): Latent TB Detection and Implications in HIV-1 Infected Women and Their Children Tuberculosis (TB) is highly prevalent in resource-poor settings, particularly in areas with high HIV-1 prevalence. Pregnant women are at risk for progression from latent TB infection (LTBI) to active TB, mortality, and transmission of TB to their infants. Interferon-3 release assays (IGRAs) can be used to diagnose asymptomatic LTBI and, in contrast to tuberculin skin testing (TST), retains specificity in individuals who receive bacille Calmette-Guerin (BCG) vaccination. TB IGRAs have been shown to correlate well with TST testing but the predictive value of TB IGRAs for subsequent clinical disease remains undefined. Because detection of LTBI by immunodiagnostics indicate need for isoniazid (INH) prophylaxis, prospective studies to define predictive value of IGRAs are not feasible. Historical cohorts with previously accrued prospective data on TB incidence and cryopreserved peripheral blood mononuclear cells (PBMCs) offer a unique opportunity to define clinical predictive value of these immunodiagnostic tests. In addition, because current immunodiagnostics do not cross-react with BCG, they offer, for the first time, an opportunity to characterize LTBI in BCG-exposed infants and children. We propose to use a historical cohort of >400 HIV-1 infected mothers and their children from Nairobi, Kenya to determine the prevalence and correlates of LTBI detection using IGRAs. Serial data on clinical TB, mortality, CD4 change, and HIV-1 RNA during 1-2 year postpartum follow-up is available for mothers and infants in this cohort. Thus, we will determine prevalence, correlates, and predictive value of IGRA- detected LTBI during pregnancy on prospective postpartum incidence of active TB, HIV- 1 progression, and mortality in women and children. In addition, we propose to determine incidence of LTBI as detected by IGRAs in women and children during the postpartum period. The proposed study will efficiently obtain important data on TB pathogenesis and immunodiagnostic testing in HIV-1 co-infected women and their children necessary for development of new TB prevention efforts in these populations at relatively high risk for TB. PUBLIC HEALTH RELEVANCE The proposed study will efficiently obtain important data on TB pathogenesis and immunodiagnostic testing in HIV-1 co-infected women and their children necessary for development of new TB prevention efforts in these populations at relatively high risk for TB