Impact of Immune Changes of HIV and Stages of Pregnancy on Tuberculosis

Post Date: 
2014-09-01
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Summary: 
This is the Parent Study for CCGHE’s PRACHITI (PRegnancy And CHanges In TuberculosIs) effort. It's supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development at the U.S. National Institutes of Health. 
 
Purpose: TB is a leading cause of maternal mortality, especially among HIV-infected women. Women are most likely to develop active TB during and immediately after pregnancy. The immunologic conditions responsible for this phenomenon are not understood. Our recent research shows that pregnant women with a positive interferon gamma release assay (IGRA) have diminished IFN-γ responses to Mycobacterium tuberculosis (MTB)-specific antigens during the third trimester and return to baseline 3-6 months postpartum. The purpose of this study is to study the immune response to MTB-specific antigens at different stages of pregnancy and impact on maternal-infant outcomes. 
 
Design: A prospective longitudinal cohort study of HIV-infected and HIV-uninfected mother-infant pairs. Pregnant women will be enrolled from the antenatal clinic at Sassoon Hospital in Pune, India, during their second trimester with additional visits at third trimester, delivery, 6 weeks, 3, 6, 12, 18 and 24 months postpartum. Postpartum maternal visits will be paired with infant visits. At each visit, we will screen for active TB. During the first postpartum year, we will also collect maternal blood samples for cytokine assays, flow cytometry, and gene transcription studies. 
 
Objectives:
  1. To compare concentrations of Th1 cytokines (e.g. IFN-gamma, IL-2) before and after MTB-specific antigen stimulation in HIV-infected and –uninfected women by stage of pregnancy, including postpartum
  2. To describe the CD4+ T cell mechanism by which Th1 immune response to MTB-specific antigens is suppressed in HIV-infected and -uninfected women during pregnancy
This study will follow 4 cohorts of HIV-infected and HIV-uninfected women: 
  1. Cohort A: 200 pregnant women > 13 weeks gestational age with HIV and a positive IGRA;  
  2. Cohort B: 200 pregnant women > 13 weeks gestational age without HIV and a positive IGRA;
  3. Cohort C: 25 pregnant women > 13 weeks gestational age with HIV and a negative IGRA and negative tuberculin skin test (TST); 
  4. Cohort D: 25 pregnant women > 13 weeks gestational age without HIV and a negative IGRA and negative TST.

Infants born to mothers enrolled in the study will also be followed for the duration of the study. 

 

Collaborators: 
  • Weill-Cornell Medical College, New York, NY
  • University of Texas