Key Dates

Related Announcements

May 07, 2020 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed). See NOFO PA-20-195.

May 05, 2020 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed). See NOFO PA-20-185.

May 05, 2020 - Research Project Grant (Parent R01 Basic Experimental Studies with Humans Required). See NOFO PA-20-184.

Issued by

National Institute of Dental and Craniofacial Research (NIDCR)

Purpose

The National Institute of Dental and Craniofacial Research (NIDCR) is issuing this Notice of Special Interest (NOSI) to encourage innovative and multi-disciplinary basic and translational research to elucidate the mechanisms of, and strategies for, addressing HIV pathogenesis, HIV-associated comorbidities, co-infections, and complications in the oropharyngeal cavity. 

Background:

It is estimated that 1.2 million persons in the United States were living with diagnosed and undiagnosed HIV at the end of 2022. New HIV infections decreased by 12% from 36,300 in 2018 to 31,800 in 2022, most likely driven by the increased use of pre-exposure prophylaxis (PrEP) among young people. Well-tolerated, long-acting antiretroviral therapy (ART) has enhanced health and quality of life and reduced incidence and mortality in people living with HIV (PLWH). The perinatal ART prophylaxis also helped mother-to-child transmission (MTCT) significantly, yet approximately 10% of children 14 years and younger acquire HIV during gestation, childbirth, or breastfeeding through the oral mucosa and tonsillar tissues.

Oropharyngeal tissues are key sources of HIV-related comorbidities, coinfections, and complications (CCCs). It is known that oral mucosal immune homeostasis is essential in protecting HIV-associated opportunistic infections and comorbidities in PLWH. Studies suggest that behavioral and biological risk factors such as smoking, risky sexual behaviors, aging, ART, and oral diseases such as dental caries, periodontal diseases and HIV-associated salivary gland disease (HIV-SGD) may contribute to the dysbiosis of the oral microbial ecosystem and further disrupt the oral mucosal epithelial immune barrier in PLWH. In some circumstances, these co-infections lead to other severe comorbidities such as oral and oropharyngeal cancers.

Some oral malignancies in PLWH are reportedly associated with enhanced local and systemic inflammatory states and closely linked to other viruses, such as Epstein-Barr virus and Kaposi sarcoma-associated herpesvirus. It has been reported that PLWH are at two- to four-fold increased risk for oral human papillomavirus associated oropharyngeal cancers (HPV-OPC) compared with HIV-negative individuals. However, the mechanisms and pathogenic progression, such as how oral mucosal immunity and biology impact HIV and its relation to CCCs in oropharyngeal tissues, have not been fully elucidated. Moreover, untreated oral diseases in PLWH can impact their nutritional uptake, social relationships, and quality of life and, in turn, worsen overall health and HIV outcomes. To advance whole person health approaches in HIV health care and support services, there is an urgent need to better understand the relationships between oral health, overall health, and HIV status in the context of PLWH.

Scientific Areas of Interest:

Applicants responding to this NOSI should propose statistically valid, hypothesis-driven projects aimed at elucidating biological, behavioral, and/or multi-level mechanisms that facilitate HIV infection, HIV-associated comorbidities, co-infection, and complications in the oropharyngeal cavity. Multidisciplinary research is encouraged as appropriate for the proposed research.

The scope of this NOSI includes but is not limited to, the following research areas:

• Biologic mechanisms of oral HIV transmission, persistence, and latency within the oropharyngeal tissue
• Natural history and factors that may impact persistence and progression of HIV-associated oral CCCs in the context of PLWH
• Biomarkers to predict and measure HIV-related oral co-infections and comorbidities
• Mechanisms in which other comorbidities and/or medical conditions interplay with HIV-associated oral CCCs in the context of PLWH
• Oral mucosal vaccination research aiming at developing novel prophylactic oral mucosal vaccines against HIV infection
• Developing combinations of antiretroviral drugs and compounds that can be used in sustained-release formulations, in the oral cavity, for potential new PrEP strategies
• The impact of HIV treatment regimens on oral health and conditions, e.g., oral transmission in perinatal HIV, oral microbiome and HIV-associated CCCs in adolescent and adult HIV populations

Application and Submission Information

This notice applies to due dates on or after January 7, 2025, and subsequent receipt dates through January 8, 2028. 

Submit applications for this initiative using one of the following notices of funding opportunity (NOFOs) or any reissues of these announcements through the expiration date of this notice.

PA-20-195 NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed)

PA-20-185 NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)

PA-20-184 NIH Research Project Grant (Parent R01 Basic Experimental Studies with Humans Required)

Applications proposing a clinical trial that does not meet the Basic Experimental Studies with Human (BESH) definition (please see NIH’s definition of a clinical trial) must use a NOFO that allows clinical trials (please see NOT-DE-21-014 NIDCR Guidance on Applications for Investigator-Initiated Clinical Trials).

All instructions in the How to Apply - Application Guide and the notice of funding opportunity used for submission must be followed, with the following additions:

• For funding consideration, applicants must include “NOT-DE-25-038” (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

Inquiries

Please direct all inquiries to the Scientific/Research, Peer Review, and Financial/Grants Management contacts in Section VII of the listed notice of funding opportunity.

Scientific/Research Contact(s)

Hiroko Iida, DDS, MPH
National Institute of Dental and Craniofacial Research (NIDCR)
Phone: 301-594-7404
E-mail: [email protected]
 

Peer Review Contact(s)

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Financial/Grants Management Contact(s)

Gabriel Hidalgo, M.B.A.
National Institute of Dental and Craniofacial Research (NIDCR)Phone: 301-827-4630
Email: [email protected]