HIV/AIDS and Oral Health Program Division of Extramural Research
Goal
The objective of this initiative is to solicit innovative and multi-disciplinary basic, translational, and clinical research on HIV/AIDS that is relevant to dental, oral, and craniofacial (DOC) health.
Background
Despite the discovery that antiretroviral therapy (ART) substantially enhances health and quality of life and reduces incidence and mortality in People with HIV (PWH), HIV/AIDS remains as one of the world’s most serious public health challenges. At the end of 2019, an estimated 1.2 million people aged 13 and older had HIV in the United States, yet about 13% of them had not been diagnosed. In 2018, an estimated 37.9 million people worldwide were living with HIV, an increase of more than 12% in 2010 1. The ongoing HIV/AIDS epidemic is highly associated with social structural disparities including race, ethnicity, sex, gender, age, economic status, and region of residence 2. For example, nearly 2/3 of PWH are located in sub-Saharan Africa. Approximately 43% and 26% Blacks/African Americans and Hispanics/Latinx are disproportionately affected by HIV compared to other races and ethnicities, respectively. These disparities underscore the growing, unmet needs for HIV early diagnosis, prevention, treatment, and care services in these minority groups.
Advances in pre-exposure prophylaxis (PrEP) have significantly decreased mother-to-child transmission (MTCT). However, despite the perinatal ART prophylaxis, approximately 10% of children 14 years and younger acquire HIV during gestation, childbirth, or breastfeeding through the oral mucosa and tonsillar tissues 3,4. Nevertheless the biological mechanisms and prevention strategies of MTCT are poorly understood.
The DOC tissues are key sources of HIV-related comorbidities, co-infections, and complications (CCCs). It is known that oral mucosal immune homeostasis is essential in protecting HIV-associated opportunistic infections and comorbidities in PWH. Literature suggests that epidemiological and biological risk factors such as ART, smoking, aging, risky sexual behaviors 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 abrupt the oral mucosal epithelial immune barrier in PWH 5,6. In some circumstances, these co-infections ead to other severe comorbidities such as oral and oropharyngeal cancers. Some oral malignancies in PWH are 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). PWH have a two- to fourfold increased risk for oral human papillomavirus associated oropharyngeal cancers (HPV-OPC) compared with HIV-negative individuals. In addition, increased risk of oral lesions such as oral candidiasis and oral hairy leukoplakia were reported in PWH compared with HIV negative individuals 6. However, the mechanisms and pathogenic progression, such as how oral mucosal immunity and biology impact HIV and its related CCCs in oral and craniofacial tissues, have not been fully elucidated.
Moreover, poor oral health could, in turn, negatively affect overall health in PWH. Oral diseases may contribute to or combine with other comorbidities such as mental health, neurocognitive disorders, and aging. However, the way in which poor oral health status impacts overall health and the interplay with other HIV-associated comorbidities are not fully understood.
Gaps and Opportunities
This initiative builds upon the Notice of Special Interest (NOSI): Basic and Translational Oral Health Research Related to HIV/AIDS. It is seeking to foster basic, translational, and clinical research on HIV/AIDS to advance the understanding of the molecular, cellular, immunological, and genetic mechanisms and pathogenic progression of oral HIV transmission and CCCs.
This initiative will advance the FY22-25 NIH Strategic Plan for HIV and HIV-Related Research to better understand oral HIV-associated CCCs. Outcomes of this research may provide valuable insights guiding early diagnosis, development of highly efficient prevention and therapeutic strategies for oral health related CCCs in PWH. It also responds to the 2022-2026 NIDCR Strategic Plan to integrate oral and general health (priority #1).
Specific Areas of Interest
Examples of research areas that fall within the scope of this initiative include, but are not limited to:
Research on biologic mechanisms of oral HIV transmission, persistence, and latency within the oropharyngeal tissue
Clinical research on the natural history and factors that may impact persistence and progression of HIV-associated oral CCCs in the context of PWH
Basic or translational research to discover biomarkers to predict and measure HIV-related oral co-infections and comorbidities
Research exploring the mechanisms in which other comorbidities and/or medical conditions interplay with HIV-associated oral CCCs in the context of PWH
Basic or translational studies on oral mucosal vaccination research aiming at developing novel prophylactic oral mucosal vaccines against HIV infection
Basic or translational research to develop combinations of antiretroviral drugs and compounds that can be used in sustained-release formulations, in the oral cavity, for potential new PrEP strategies
Research assessing 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
Current Portfolio Overview
In the HIV/AIDS and Oral Health portfolio, some applications that align with the specific areas of interests have been collected through previous specific solicitations or investigator-initiated applications. The current initiative will sustain the momentum of research supported by NIDCR such as research-elucidating mechanisms and pathogenesis of oral HIV-associated CCCs and would allow the investigators to re-compete and renew their projects. Importantly, extending the research scope by adding clinical studies to the original focus on the basic and translational studies will help draw in new studies, especially those that have the potential to translate findings into clinical applications.
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