Dynamics of HIV-infection, Oral Innate Immunity and The Development of Oral Diseases in Children

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PROJECT SUMMARY/ABSTRACT Oral diseases are among the most prevalent non-communicable diseases (NCDs) worldwide. Salivary antimicrobial peptides (AMPs) are proteins regulated by our immune system that disrupt the membrane integrity of bacteria. Their antimicrobial activity acts on bacteria as well as some viruses and fungi. While levels of cathelicidins (LL-37) and human beta defensins (hBD 2&3) have been associated with dental caries, secretory leukocyte protease inhibitor (SLPI) has been known for inhibiting the growth of Candida albicans. There is very limited data on AMPs in young children living with HIV. In Kenya, where about 5% of the population is HIV positive, there are an estimated 105,000 infected children and adolescents aged 0-14. The University of Washington and the University of Nairobi have >20 years of NIH funding studying pediatric HIV in Kenya. This collaboration is ideally positioned to conduct this exploratory study which is aligned with PAR-21-246 to assess the extent to which HIV infection influences the occurrence and progression of oral diseases among HIV/AIDS Kenyan children and to create research capacity in global oral health by expanding current lab infrastructure to allow local analysis of salivary AMPs in the context of HIV. This longitudinal study will be conducted in a cohort of children who receive care at the Jaramogi Oginga Odinga, the largest local teaching and referral hospital in western Kenya. Over 12 months, we will recruit and follow a cohort of 300 children (3-4y) stratified by presence of HIV: a) HIV-infected (HIV+/N=100), b) HIV exposed uninfected (HEU/N=100), and c) HIV unexposed uninfected (HUU/N=100; CONTROL GROUP). We will assess participants for ART adherence, length and regimen; dental plaque; CD4; HIV-1 RNA; and additional medications. Our aims are to: 1) Describe the impact of HIV infection on the secretion of salivary antimicrobial peptides at baseline and over a 12-month follow-up period. Coinciding with current HIV schedule for medical care, we will collect unstimulated saliva (baseline, 6, and 12-month assessments) to measure a comprehensive set of AMPs: LL-37, hBDs and SLPI. By stratifying by HIV exposure (HIV+, HEU, HUU), we will be able to measure AMP levels by group and assess factors associated with secretion. 2) Determine the associations between salivary AMPs and oral diseases in the context of HIV. At baseline, 6 and 12 months of the study, we will a): assess the degree to which AMPs are associated with presence and progression of oral diseases (plus candida colony forming units, saliva flow rate and pH), within the context of HIV exposure and related treatment, and b) identify factors impacting these associations. 3) Enhance existing HIV research capacity. We will expand current human and infrastructure resources to include oral health research. While currently the study of salivary AMPs is conducted out of Kenya, we will build upon existing lab assets allowing locals to conduct these analyses, thus starting a line of research that increases Kenyan research opportunities.