Center for Clinical Research, DER, NIDCR
The objective of this concept is to encourage innovative basic and translational research into mechanisms of HIV transmission, persistence, pathogenesis and co-morbidities in the oral cavity. Research responsive to this initiative will help address gaps in our knowledge and could encourage development of improved local and systemic therapies for HIV-related oral infections and other complications in the era of combination anti-retroviral therapy (cART).
There are nearly 37 million people living with HIV/AIDS (PLWH) around the world. Approximately two million new infections occurred in 2015 (http://www.cdc.gov/hiv/basics/statistics.html). The number of infants newly infected with HIV in low and middle-income countries was estimated at 240,000 in 2013 (http://apps.who.int/iris/bitstream/10665/128196/1/WHO_HIV_2014.15_eng.pdf?ua=1). At least a third of these cases are due to continuous breastfeeding and viral transfer across the oral mucosa and tonsillar tissue. The mechanisms of this transfer are not fully understood 1.
cART has reduced the morbidity and substantially decreased the mortality associated with HIV infections 2-3. Some oral mucosal diseases that were closely associated with low CD4 count and higher plasma viral load, such as oral candidiasis and hairy leukoplakia, are less frequent in patients on cART4. However, other conditions such as oral and salivary gland diseases associated with HIV and human papilloma virus (HPV) have not decreased in frequency in PLWH on cART5. The reasons these conditions have not decreased in prevalence with cART has not been elucidated.
Severe forms of periodontitis and dental caries are reported in PLWH, along with changes in oral microbiota. However, it is unclear if these changes in the microbiota are responsible for disease severity6-8. Some reports also indicate that PLWH develop immune reconstitution inflammatory syndrome (IRIS) that is manifested as Sjögrens syndrome-like symptoms, with xerostomia and inflammation of the salivary glands9-10.
Selected oral malignancies in PLWH are reported to be related to enhanced local and systemic inflammatory state and are closely linked to other viral conditions, such as Epstein Barr Virus and Kaposi’s sarcoma herpes virus. However, the mechanisms of co-morbidity are not fully understood 11-12.
Gaps and Opportunities
This initiative is seeking to support basic and translational research to advance our understanding of the molecular and cellular mechanisms of disease onset and progression in the oral cavity related to HIV/AIDS. Applications should propose statistically valid, hypothesis-driven or hypothesis-generating, evidence-based projects aimed at elucidating molecular and cellular mechanisms that facilitate HIV infection or alterations by HIV, leading to accelerated progression of various oral pathologies.
Alignment with Institute Goals and Strategic Plan
This initiative is aligned with the NIDCR Strategic Plan 2014-2019, Goal I, “Support the best science to improve dental, oral, and craniofacial health”. Specifically, the initiative aligns with objectives I-1 and I-3, to “Enable basic research to advance knowledge of dental, oral, and craniofacial health” and to “Conduct translational and clinical investigations to improve dental, oral, and craniofacial health.”
Research topics supported by this initiative could include, but are not limited to:
- Mechanisms of mother to child oral HIV transmission.
- Oral mucosa defense mechanisms in the context of HIV infection and cART.
- Mechanisms of oral HIV/AIDS prophylactic and therapeutic vaccination.
- HIV and the oral microbiome.
- Mechanisms leading to the development of caries and periodontitis in PLWH.
- Oral co-morbidities in PLWH.
Current Portfolio Overview
Basic and translational studies in oral HIV/AIDS are currently supported by the Program. Most of these projects were jumpstarted through specific previous solicitations. The current initiative, broad in scope, will sustain the momentum of research that we are supporting and allow the investigators to re-compete and renew their projects. This initiative will also draw in new studies in topics there are less represented in the portfolio, e.g. mother-to-child oral HIV transmission.
- Moussa S, Jenabian MA, Gody JC, Léal J, Grésenguet G, Le Faou A, Bélec L. Adaptive HIV-Specific B Cell-Derived Humoral Immune Defenses of the Intestinal Mucosa in Children Exposed to HIV via Breast-Feeding. PLoS One. 2013; 8(5).
- Springer SA, Dushaj A, Azar MM. The impact of DSM-IV mental disorders on adherence to combination antiretroviral therapy among adult persons living with HIV/AIDS: a systematic review. AIDS Behav. 2012 Nov;16(8):2119-43.
- Crum NF, Riffenburgh RH, Wegner S, Agan BK, Tasker SA, Spooner KM, Armstrong AW, Fraser S, Wallace MR; Triservice AIDS Clinical Consortium. Comparisons of causes of death and mortality rates among HIV-infected persons: analysis of the pre-, early, and late HAART (highly active antiretroviral therapy) eras J Acquir Immune Defic Syndr. 2006 Feb 1;41(2):194-200.
- Sharma G, Pai MK, Nagpal A. Prevalence of Oral Manifestations and Their Association with CD4/CD8 Ratio and HIV Viral Load in South India. Int J Dent. 2011; 2011: 964278.
- Speicher DJ, Ramirez-Amador V, Dittmer DP, Webster-Cyriaque J, Goodman MT, Moscicki AB. Viral infections associated with oral cancers and diseases in the context of HIV: a workshop report. Oral Dis. 2016 Apr;22 Suppl 1:181-92.
- Jordan L. Periodontal pathogens and reactivation of latent HIV infection: a review of the literature. J Dent Hyg. 2013 Apr;87(2):59-63.
- Noguera-Julian M, Guillén Y, Peterson J, Reznik D, Harris EV, Joseph SJ, Rivera J, Kannanganat S, Amara R, Nguyen ML, Mutembo S, Paredes R, Read TD, Marconi VC. Oral microbiome in HIV-associated periodontitis. Medicine (Baltimore). 2017 Mar;96(12).
- Valentine J, Sanders AE, Saladyanant T, Ramsey K, Blake J, Morelli T, Southerland J, Quinlivan EB, Nelson J, DeParis K, Webster-Cyriaque J. Impact of Periodontal Intervention on Local inflammation, Periodontitis and HIV Outcomes. Oral Dis. 2016 Apr;22 Suppl 1:87-97.
- The diffuse infiltrative lymphocytosis syndrome (DILS). A comprehensive review. Ghrenassia E, Martis N, Boyer J, Burel-Vandenbos F, Mekinian A, Coppo P. J Autoimmun. 2015 May; 59:19-25.
- Nikolaos VS, Gamaletsou MN, Moutsopoulos HM. Is Sjögren's syndrome a retroviral disease? Arthritis Res Ther. 2011; 13(2): 212.
- Kamat RD, Dhupar V, Akkara F, Dhupar A. HIV-associated large aggressive extranodal lymphoma of the oral cavity. Natl J Maxillofac Surg. 2016 Jul-Dec;7(2):205-208.
- Gloghini A, Dolcetti R, Carbone A. Lymphomas occurring specifically in HIV-infected patients: from pathogenesis to pathology. Semin Cancer Biol. 2013 Dec;23(6):457-67.