Longitudinal Oral Microbiome for HIV/HEU/HUU Children Aged 3-4 in Western Kenya

ABSTRACT As of 2022, HIV infection and HIV-related diseases remain among the leading causes of death for children under five, despite the availability of antiretroviral therapy (ART). Children living in Sub-Saharan Africa face the highest mortality rate, with approximately 1 in 13 children dying before reaching their fifth birthday. Moreover, HIV-

exposed uninfected (HEU) children (exposed in utero or during breastfeeding) have a higher mortality rate, more frequent hospitalizations, and more severe manifestations of diseases compared to those who are HIV- unexposed uninfected (HUU). It is estimated that there are 15.4 million HEU infants worldwide, with 90% of them

living in sub-Saharan Africa. Cross-sectional age-stratified analyses have shown that the bacterial community composition in the saliva of HEU children changes from being similar to HIV-infected children under three years old to being similar to HUU children at age four and older. Furthermore, the incidence of oral diseases increases

remarkably with age, which might be related to the development of oral microbiota. We hypothesize that the oral microbiome of HIV-exposed uninfected (HEU) children changes significantly during primary dentition (age 3-5-years) compared to the other two groups, children who are HIV-positive and in care

(HIC) and those who are HIV-unexposed uninfected (HUU) during one year of follow-up. In this R03 study, we will collect oral swab samples from 360 children at three visits (1,080 samples in total). Duplicate samples will be collected and stored for future use. This proposed study focuses on the one-year change in the oral

microbiome during the primary dentition stage among three cohorts in Kisumu County. Kisumu is one of the poorest regions in Western Kenya and has the third-highest prevalence of HIV/AIDS (19.3%) among children (0- 14-years of age) in Kenya. The research will leverage an important effort (parent study, R21TW012033) aimed

at studying the dynamics of HIV progression and oral diseases. The proposed R03 study will provide the foundation for potential precise microbiota-targeted interventions to improve oral health-related outcomes among HEU children. Meanwhile, this study will strengthen the capacity and infrastructure for integrating both medical

and dental care among HIV and HEU children in Kisumu, serving as an example of care for resource-limited areas. This study will also provide valuable preliminary data for an investigator-initiated R01 research project that aims to implement microbiome-based care into the routine care of HEU children. We will analyze the

samples using 16S ribosomal RNA (16S rRNA) at the V4 region. This way, we can compare our results with samples collected in other regions using the same method. Additionally, we use 16S rRNA because it is the most cost-effective approach for a large number of samples and is easily scalable to resource-limited regions.