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Understanding the Impact of Lower Dose Medroxyprogesterone Acetate on Female Genital Tract Microbiome and Immunology

Award Number: R01HD096937
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary The progestin-only contraceptive Depo-Provera 150mg delivered intramuscularly (150-IM), the most widely used injectable contraceptive worldwide, has been associated with increased HIV acquisition in many observational studies. The absence of causal evidence from randomized clinical trials has resulted in uncertainty about whether the observed association is due to methodological limitations or a real biological effect. Due to this uncertainty, and the risks associated with unplanned pregnancies, the World Health Organization advises that women at high risk of HIV can continue to use progestin injectables with counseling. Data on the effects of other long-acting contraceptives on HIV acquisition, such as implants and intrauterine devices (IUDs) are even more scarce; and there are no data on Sayana® Press (DMPA-SQ 104mg, hereafter 104-SQ) and other lower dose DMPA formulations in development. This study will leverage three ongoing randomized trials to conduct timely, innovative, and cost efficient research to evaluate the impact of multiple contraceptives – including 150-IM, the levonorgestrel (LNG) implant, the copper IUD, 104- SQ, and novel low dose DMPA formulations - on the female genital tract (FGT) microbial and immune environment. The aims of this research are to: 1) analyze the vaginal microbiome of women by 16S rRNA gene survey and metagenomic sequencing for high-resolution analysis of bacteria, viruses, fungi, and parasites before and after initiation of 150-IM, 104-SQ, LNG implant or Cu-IUD; 2) evaluate levels of vaginal cytokines and antimicrobial proteins before and after initiation of 150-IM, 104-SQ, LNG implant or Cu-IUD; 3) evaluate changes in the frequency and activation of CCR5+, CCR6+CCR10- (Th17-like) and a4ß7 CD4+ T cells in the cervix among women using 150-IM, 104-SQ, LNG implant or Cu-IUD; 4) evaluate changes in the vaginal microbiome, cytokines and antimicrobial proteins with use of lower MPA doses (45, 75 and 105mg) compared to 150-IM, and the effect of systemic and genital endogenous and exogenous hormone levels on these outcomes; and 5) conduct a discovery metaproteomics analysis to evaluate alterations in vaginal human and microbial proteins following initiation of 150-IM, 104-SQ, LNG implant or Cu-IUD. This research will clarify the complex associations between contraceptive exposure, endogenous and exogenous hormones and the FGT microbiome, markers of immunity and inflammation, recruitment of HIV target cells and activation of those cells and markers of epithelial barrier repair. These data will inform contraceptive use and policy as well as provide targets and safety endpoints for the development of future contraceptives. Moreover, these data will provide the first evidence of FGT microbiome and immune changes that occur following initiation of other MPA based contraceptives, including 104-SQ and novel low dose MPA formulations which will be critically needed if the ECHO trial identifies increased acquisition of HIV among 150-IM users.


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: 2023 ( Subtotal = $0 )
2023	2022	FAMILY HEALTH INTERNATIONAL	359 BLACKWELL STREET	DURHAM	NC	27701	DURHAM	USA	Child Health and Human Development Extramural Research	000	5	4/3/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $642,449 )
2022	2022	FAMILY HEALTH INTERNATIONAL	359 BLACKWELL ST STE 200	DURHAM	NC	27701	DURHAM	USA	Child Health and Human Development Extramural Research	000	5	5/25/2022	NON-COMPETING CONTINUATION	$642,449
														Subtotal = $642,449

Issue Date FY: 2021 ( Subtotal = $1,213,310 )
2021	2021	FAMILY HEALTH INTERNATIONAL	359 BLACKWELL ST STE 200	DURHAM	NC	27701	DURHAM	USA	Child Health and Human Development Extramural Research	003	4	9/2/2021	SUPPLEMENT FOR EXPANSION	$612,303
2021	2021	FAMILY HEALTH INTERNATIONAL	359 BLACKWELL ST STE 200	DURHAM	NC	27701	DURHAM	USA	Child Health and Human Development Extramural Research	002	4	8/27/2021	NON-COMPETING CONTINUATION	$12,021
2021	2021	FAMILY HEALTH INTERNATIONAL	359 BLACKWELL ST STE 200	DURHAM	NC	27701	DURHAM	USA	Child Health and Human Development Extramural Research	001	4	7/13/2021	NON-COMPETING CONTINUATION	$0
2021	2021	FAMILY HEALTH INTERNATIONAL	359 BLACKWELL ST STE 200	DURHAM	NC	27701	DURHAM	USA	Child Health and Human Development Extramural Research	000	4	6/9/2021	NON-COMPETING CONTINUATION	$588,986
														Subtotal = $1,213,310

Issue Date FY: 2020 ( Subtotal = $602,299 )
2020	2020	FAMILY HEALTH INTERNATIONAL	359 BLACKWELL ST STE 200	DURHAM	NC	27701	DURHAM	USA	Child Health and Human Development Extramural Research	000	3	6/3/2020	NON-COMPETING CONTINUATION	$602,299
2020	2020	FAMILY HEALTH INTERNATIONAL	359 BLACKWELL ST STE 200	DURHAM	NC	27701	DURHAM	USA	Child Health and Human Development Extramural Research	001	3	8/6/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $602,299

Issue Date FY: 2019 ( Subtotal = $620,338 )
2019	2019	FAMILY HEALTH INTERNATIONAL	359 BLACKWELL ST STE 200	DURHAM	NC	27701	DURHAM	USA	Child Health and Human Development Extramural Research	002	2	6/6/2019	NON-COMPETING CONTINUATION	$575,173
2019	2018	FAMILY HEALTH INTERNATIONAL	359 BLACKWELL ST STE 200	DURHAM	NC	27701	DURHAM	USA	Child Health and Human Development Extramural Research	001	1	11/15/2018	NEW	$0
2019	2018	FAMILY HEALTH INTERNATIONAL	359 BLACKWELL ST STE 200	DURHAM	NC	27701	DURHAM	USA	Child Health and Human Development Extramural Research	003	1	9/13/2019	NEW	$0
2019	2018	FAMILY HEALTH INTERNATIONAL	359 BLACKWELL ST STE 200	DURHAM	NC	27701	DURHAM	USA	Child Health and Human Development Extramural Research	000	1	10/29/2018	NEW	$45,165
														Subtotal = $620,338

Issue Date FY: 2018 ( Subtotal = $609,470 )
2018	2018	FAMILY HEALTH INTERNATIONAL	359 BLACKWELL ST STE 200	DURHAM	NC	27701	DURHAM	USA	Child Health and Human Development Extramural Research	000	1	9/18/2018	NEW	$609,470
														Subtotal = $609,470

Grand Total All Awards = $3,687,866

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Understanding the Impact of Lower Dose Medroxyprogesterone Acetate on Female Genital Tract Microbiome and Immunology

Award Number: R01HD096937

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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