November 23, 2021
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)
National Institute of Dental and Craniofacial Research (NIDCR)
The National Institute of Dental and Craniofacial Research (NIDCR) is issuing this Notice of Special Interest (NOSI) to encourage basic and translational research into mechanisms of HIV transmission, persistence, and pathogenesis in the oral cavity and its associated co-morbidities.
In 2018, an estimated 37.9 million people worldwide were living with HIV, an increase of more than 12 percent from 33.4 million people in 2010. This is the result of both continued new infections and people living longer with HIV. Overwhelming evidence that suppression of viral replication controls disease progression and human transmission has led to universal recommendations for antiretroviral therapy (ART) in people living with HIV (PLWH). Yet, only 62 percent of PLWH were accessing ART at the end of 2018, and 86 percent of those using ART had suppressed viral load.
Oral mucosa comprises many host immune cells and reportedly is a rare site for HIV transmission. With advances in perinatal HIV intervention strategies, less than 1% of new HIV diagnoses in the US were due to mother-to-child transmission (MTCT) in 2018. However, the risk of HIV transmission through breastfeeding and viral transfer across the oral mucosa and tonsillar tissues can occur despite perinatal ART prophylaxis, and one-third to one-half of all infant HIV infections worldwide are reportedly through breastfeeding. While the oral epithelium is one of the first sites exposed to HIV through breastfeeding, the molecular mechanisms of MTCT are not fully understood.
Despite decreased incidence in the era of ART, oral mucosal diseases such as oral candidiasis and oral hairy leukoplakia remain common in the context of low CD4 count and higher plasma viral load. Some oral malignancies in PLWH are also reportedly related to enhanced local and systemic inflammatory states and are closely linked to other viruses, such as Epstein Barr Virus and Kaposi sarcoma-associated herpesvirus (human herpesvirus 8). Further, human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinomas are among the most common HPV-related cancers in the US, and due to reasons that remain unknown, PLWH have anywhere from a 2 to 4-fold increased risk for the disease compared to HIV-negative individuals.
Some reports also indicate that PLWH develop immune reconstitution inflammatory syndrome (IRIS) that manifests as infectious (e.g. oral candidiasis) and non-infectious conditions such as recurrent oral ulcers and parotid enlargement after the initiation of ART. Yet, its etiology and the host risk factors for the innate immune dysfunction associated with ART remain poorly understood. Furthermore, the roles of and mechanisms by which mucosal immunity, salivary cytokines, and the oral microbiota influence HIV pathogenesis and/or the natural history of acquisition and persistence of co-infections and opportunistic infections in oral cavity have not been elucidated.
Dental caries and severe forms of periodontitis are reported in PLWH, along with changes in the oral microbiota. However, there are gaps in our knowledge about the pathogenesis and progression of these common oral diseases in the context of HIV and ART and how oral microbial and mucosal ecosystems are influenced by local and systemic HIV-associated factors. In addition, the role of periodontal inflammation on HIV or other virus acquisition, persistence, and transmission are not well understood.
Scientific Areas of Interest
Applicants responding to this NOSI should propose statistically valid, hypothesis-driven projects aimed at elucidating molecular and cellular mechanisms that facilitate HIV infection or alterations by HIV, leading to onset and accelerated progression of various oral pathologies. 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:
Application and Submission Information
NIDCR encourages applicants to use the following FOAs in response to this NOSI:
Applications proposing a clinical trial (please see NIH’s definition of a clinical trial) must use an FOA that allows clinical trials (please see NOT-DE-21-004 NIDCR Guidance on Applications for Investigator-Initiated Clinical Trials).
To respond to this NOSI, projects must choose a specific topic that is aligned with Office of AIDS Research (OAR) priority areas as described in NOT-OD-20-018. Applications that do not have any focus on or inclusion of HIV will be considered not responsive to this NOSI.
This notice applies to due dates on or after January 7, 2022 and subsequent receipt dates through May 8, 2023.
All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:
Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.
Hongen Yin, MD, PhD, MHSc
National Institute of Dental and Craniofacial Research
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)
Diana Rutberg, MBA
National Institute of Dental and Craniofacial Research