Sunday, November 24, 2024 11/24/2024

Combination biomarkers for preventing HIV and adverse birth outcomes in a South African pregnancy cohort: implications for infant health

Award Number: R01HD102052
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By:

View Award Abstract

Abstract Young pregnant women are at extremely high risk for acquiring HIV in late pregnancy and postpartum. Although the precise mechanisms to explain the high risk of HIV during this time period is unknown, highly diverse vaginal microbial communities and elevated genital inflammation have been associated with increased HIV susceptibility among non-pregnant women. A balanced maternal inflammatory milieu and a Lactobacillus dominated vaginal microbial communities have long been associated with optimal pregnancy outcomes. However, untimely or excessive inflammatory response or diverse microbial communities in the vagina can lead to adverse birth outcomes and/or HIV acquisition in at risk women. With heightened risk of HIV in pregnancy and postpartum, pre-exposure prophylaxis (PrEP) is increasingly being used during these periods but the effects of maternal PrEP use on child health outcomes remains underexplored. Here, we propose to use two unique cohorts of HIV- uninfected pregnant women and their infants from Umlazi, KwaZulu-Natal, including those actively taking PrEP, to better understand their risk factors for adverse birth outcomes and HIV acquisition as well as neonatal morbidity. The specific aims are to: 1) assess whether vaginal microbial taxa or cytokines during gestation predict risk of preterm labor and delivery in women at high risk for HIV. 16S rRNA gene sequencing and multiplex bead arrays will be used to characterize the composition of vaginal microbial communities and soluble biomarkers of genital inflammation in cervicovaginal swabs and SoftCup fluids collected from women at ~12.5-21.5 weeks’ gestation and relate these to incident preterm labor and delivery; 2) determine whether increased vaginal microbial diversity and/or inflammation could explain the higher HIV risk during late pregnancy and early postpartum. Microbial communities and cytokines from cervicovaginal swabs and SoftCup fluids collected at 14- 28 weeks’ gestation will be compared with those collected late pregnancy (38–40 weeks’ gestation) and 14 and 26 weeks postpartum to identify potential drivers of increased susceptibility HIV infection during these periods; and 3) to determine the effects of antiretroviral exposure during gestation and breastfeeding on infant glucose metabolism and innate immunity. Using samples collected from HIV-unexposed infants at 6 weeks and 12 months of age, plasma adipokine and cytokine levels and markers of insulin resistance will be compared in antiretroviral (ARV)-exposed versus unexposed infants. The proposed research is innovative and will, for the first time, determine whether specific vaginal anaerobic microbes and associated inflammation can predict which women will deliver preterm or acquire HIV in our setting. Further, unique cohorts are available to examine the immunological and metabolic effects of maternal ARV use during pregnancy on infant health without HIV exposure, to inform risk-benefit analyses of maternal PrEP. This study has the potential to lead to more refined interventions to mitigate risks of adverse birth outcomes, HIV acquisition and neonatal morbidity.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $278,459 )
2024	2024	CENTRE FOR THE AIDS PROGRAM OF RESEARCH IN SOUTH AFRICA	719 UMBILO ROAD	DURBAN				ZAF	Child Health and Human Development Extramural Research	002	5	6/5/2024	NON-COMPETING CONTINUATION	$2,785
2024	2024	CENTRE FOR THE AIDS PROGRAM OF RESEARCH IN SOUTH AFRICA	719 UMBILO ROAD	DURBAN				ZAF	Child Health and Human Development Extramural Research	001	5	5/7/2024	NON-COMPETING CONTINUATION	$25,061
2024	2024	CENTRE FOR THE AIDS PROGRAM OF RESEARCH IN SOUTH AFRICA	719 UMBILO ROAD	DURBAN				ZAF	Child Health and Human Development Extramural Research	000	5	3/27/2024	NON-COMPETING CONTINUATION	$250,613
														Subtotal = $278,459

Issue Date FY: 2023 ( Subtotal = $312,989 )
2023	2023	CENTRE FOR THE AIDS PROGRAM OF RESEARCH IN SOUTH AFRICA	719 UMBILO ROAD	DURBAN				ZAF	Child Health and Human Development Extramural Research	000	4	3/15/2023	NON-COMPETING CONTINUATION	$312,989
														Subtotal = $312,989

Issue Date FY: 2022 ( Subtotal = $325,543 )
2022	2022	CENTRE FOR THE AIDS PROGRAM OF RESEARCH IN SOUTH AFRICA	719 UMBILO ROAD	DURBAN				ZAF	Child Health and Human Development Extramural Research	000	3	5/19/2022	NON-COMPETING CONTINUATION	$325,543
														Subtotal = $325,543

Issue Date FY: 2021 ( Subtotal = $328,064 )
2021	2021	CENTRE FOR THE AIDS PROGRAM OF RESEARCH IN SOUTH AFRICA	719 UMBILO ROAD	DURBAN				ZAF	Child Health and Human Development Extramural Research	000	2	4/2/2021	NON-COMPETING CONTINUATION	$328,064
														Subtotal = $328,064

Issue Date FY: 2020 ( Subtotal = $339,141 )
2020	2020	CENTRE FOR THE AIDS PROGRAM OF RESEARCH IN SOUTH AFRICA	719 UMBILO ROAD	DURBAN		4001		ZAF	Child Health and Human Development Extramural Research	000	1	4/3/2020	NEW	$339,141
														Subtotal = $339,141

Grand Total All Awards = $1,584,196

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Combination biomarkers for preventing HIV and adverse birth outcomes in a South African pregnancy cohort: implications for infant health

Award Number: R01HD102052

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer