# HIV, gestational diabetes and TB in pregnancy

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2024 · $687,723

## Abstract

ABSTRACT: Tuberculosis (TB) is a leading cause of maternal mortality worldwide, especially among women
with HIV. Of the 1.3 million pregnant women living with HIV, 85% use combined anti-retroviral therapy (cART),
which should significantly decrease their risk of TB. Yet pregnant women with well-controlled HIV still have a 2-
3 times greater incidence of TB than pregnant women without HIV. There is an urgent need to identify the
immune impairment responsible for the increased risk of TB in these women.
Gestational diabetes (GDM)– which affects 16% of pregnancies globally, and up to 40% of pregnancies in TB-
endemic India–likely contributes to the increased risk of TB in pregnancy, especially for women with HIV. We
base this hypothesis on the known association between HIV, diabetes (DM) and TB in non-pregnant
populations and our preliminary data on HIV, GDM and TB in pregnancy. We found HIV increases GDM
prevalence, and GDM impairs the host immune response to M. tuberculosis (Mtb).
In partnership with BJ Government Medical College in India (BJGMC), we propose a longitudinal study to fully
describe HIV’s effect on GDM risk, and GDM’s effect on the immune response to MTB in pregnancy. BJGMC
has conducted NIH clinical research for over 20 years with expertise in HIV and TB in pregnancy. We will enroll
2nd trimester women from the antenatal clinic at BJGMC in Pune, India, with additional visits at 3rd trimester,
delivery, 6 weeks, 6 months, and 12 months postpartum. Women will be screened for GDM at enrollment with
an oral glucose tolerance test. A subset comprised of all women diagnosed with GDM, and a matched number
of women without GDM, will have additional blood and placenta samples collected for flow cytometry and
cytokine studies. Enrolled women will be screened for active TB at each visit. Our specific aims are to:
1. Determine the effect of chronic HIV-induced inflammation on glucose metabolism during pregnancy
 and GDM prevalence. We hypothesize that women with HIV will have double the prevalence of GDM
 compared to women without HIV. We further hypothesize that elevated plasma TNF-a levels and decreased
 placental GLUT4 will be associated with GDM in women with HIV.
2. Determine the effect of GDM on the CD4+ and CD8+ T-cell response to Mtb and incident TB. We
 hypothesize that women with GDM will have a significantly higher incidence of active TB than women
 without GDM. We hypothesize that women with GDM will have suppressed Mtb-specific memory CD4+ and
 CD8+ T-cell function, with a decreased ability to activate macrophages, compared to women without GDM.
This will be the first study to determine if the pathophysiology of GDM is different in women with HIV and to
delineate the TB-specific clinical and immune sequelae of GDM for pregnant women. The results of this study
will identify pregnant women at the highest risk for active TB, improve targeted GDM screening and TB
prevention and potentially identify novel targets for GDM prevention and ...

## Key facts

- **NIH application ID:** 10869955
- **Project number:** 5R01AI162235-03
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Jyoti S Mathad
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $687,723
- **Award type:** 5
- **Project period:** 2022-07-15 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10869955

## Citation

> US National Institutes of Health, RePORTER application 10869955, HIV, gestational diabetes and TB in pregnancy (5R01AI162235-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10869955. Licensed CC0.

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