Monday, January 13, 2025 1/13/2025

How sex, host microenvironment, and immune responses shape acquisition of genital bacteria that increase HIV risk

Award Number: R01DK131936
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY Recently, several genital anaerobic bacteria that are not classically associated with sexually transmitted infections (non-STI) were linked to increased heterosexual transmission of HIV, likely by inducing immune responses that enhances HIV target cell activation and recruitment to the genital mucosa. This project seeks to close critical knowledge gaps regarding acquisition and persistent carriage of this new HIV risk factor. Our long-term goals are to elucidate the determinants of genital microbiome composition and the biological mechanisms that link genital bacteria to host susceptibility to HIV, and to leverage this knowledge to develop innovative solutions to prevent HIV. The objective is to understand the heterosexual transmission dynamics of genital bacteria associated with HIV risk and to determine the abiotic and biotic factors that impact acquisition and persistence of these genital bacteria in men. Our central hypothesis is that perturbations affect penile microbiome composition—including acquisition, loss, or persistence of genital bacteria associated with HIV risk—predictably based a set of abiotic and biotic factors. The rationale for this project is that, by understanding the abiotic and biotic factors that determine acquisition, loss, or persistence of specific genital bacteria, we will be able to identify and develop new strategies to prevent or reduce colonization. Aim 1. Elucidate the sexual transmission of genital bacteria and the determinants of the penile microbiome after sex. We will test this by: (i) Characterize the genital bacteria strains present in adolescent boys before and after sexual debut (n = 200) and (ii) Determine the effect of pre-coital host (penile) and partner (vaginal) genital pH, oxygenation, moisture, metabolites, anti-bacteria IgA, and microbiome on the acquisition or persistence (1, 8, and 72 hour post-sex) of genital bacteria in the host (n = 106 couples). Aim 2. Elucidate the determinants of the penile microbiome after antimicrobial treatment. We will test this by comparing pre- and post- treatment (Day 3, 8, and 28) penile microbiomes in 1 control arm and 4 treatment arms, including 3 topical treatments: (i) 2% clindamycin, (ii) 1% H2O2, (iii) 0.75% metronidazole, and (iv) oral tinidazole. Aim 3. Validate the impact of abiotic and biotic factors on the penile microbiome response to perturbation using an in vitro model. We will achieve this aim by adding: (i) donor vaginal microbiome and (ii) topical antimicrobials to penile microbiome in organotypic foreskin model to assess the effect of abiotic factors and bacterial strains on microbiome outcome. The proposed research is innovative, in our opinion, because it represents a departure from the status quo by elucidating transmissible dysbiosis, and doing so with absolute abundance metrics, innovative study designs, and a novel co-culture model. The proposed research is significant because it is expected to reveal how sex and antimicrobials impact penile microbiome and what drives outcome.


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: 2025 ( Subtotal = $548,107 )
2025	2025	GEORGE WASHINGTON UNIVERSITY (THE)	1918 F ST NW	WASHINGTON	DC	20052	DISTRICT OF COLUMBIA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	11/21/2024	NON-COMPETING CONTINUATION	$548,107
														Subtotal = $548,107

Issue Date FY: 2024 ( Subtotal = $596,262 )
2024	2024	GEORGE WASHINGTON UNIVERSITY (THE)	1918 F ST NW	WASHINGTON	DC	20052	DISTRICT OF COLUMBIA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	11/30/2023	NON-COMPETING CONTINUATION	$558,997
2024	2024	GEORGE WASHINGTON UNIVERSITY (THE)	1918 F ST NW	WASHINGTON	DC	20052	DISTRICT OF COLUMBIA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	3	5/24/2024	NON-COMPETING CONTINUATION	$37,265
														Subtotal = $596,262

Issue Date FY: 2023 ( Subtotal = $614,209 )
2023	2023	GEORGE WASHINGTON UNIVERSITY, THE	1918 F ST NW	WASHINGTON	DC	20052	DISTRICT OF COLUMBIA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	12/21/2022	NON-COMPETING CONTINUATION	$552,789
2023	2023	GEORGE WASHINGTON UNIVERSITY, THE	1918 F ST NW	WASHINGTON	DC	20052	DISTRICT OF COLUMBIA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	1/5/2023	NON-COMPETING CONTINUATION	$61,420
														Subtotal = $614,209

Issue Date FY: 2022 ( Subtotal = $629,204 )
2022	2022	GEORGE WASHINGTON UNIVERSITY, THE	1918 F ST NW	WASHINGTON	DC	20052	DISTRICT OF COLUMBIA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	2/1/2022	NEW	-$25,033
2022	2022	GEORGE WASHINGTON UNIVERSITY, THE	1918 F ST NW	WASHINGTON	DC	20052	DISTRICT OF COLUMBIA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	1	6/2/2022	NEW	$0
2022	2022	GEORGE WASHINGTON UNIVERSITY, THE	1918 F ST NW	WASHINGTON	DC	20052	DISTRICT OF COLUMBIA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	11/29/2021	NEW	$654,237
														Subtotal = $629,204

Grand Total All Awards = $2,387,782

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How sex, host microenvironment, and immune responses shape acquisition of genital bacteria that increase HIV risk

Award Number: R01DK131936

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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