Oral Inflammation and Systemic Immune Activation Among Children Living with HIV in Kenya

Abstract

Oral Inflammation and Systemic Immune Activation Among Children Living with HIV in Kenya John Sumkai Atiiga Chair of Supervisory Committee:Jennifer Slyker Department of Global Health BackgroundPoor oral health can lead to chronic pain, decreased nutritional intake, lower quality of life, and increased risk of systemic inflammation-related diseases. Children living with HIV (CLHIV) have an elevated risk for oral diseases, including gingivitis, which is incompletely resolved with antiretroviral treatment (ART). Oral inflammation may be an important contributor to systemic inflammation in CLHIV, and an attractive target for intervention. The goal of this study was to assess associations between early-life HIV infection and oral inflammation after over 10 years of ART, and to assess whether oral inflammation was associated with systemic inflammation and immune activation. Methods This nested study involved two Kenyan cohorts of CLHIV: a “later-treated” cohort enrolled at ages 15 months to 12 years with ART initiated according to clinical stage/CD4 criteria, and an “early-treated” cohort enrolled below 1 year old, with immediate ART initiation. Bleeding on Probing score (BOP score) was calculated during an oral examination to quantify the percentage of sites with gingivitis. The enzyme-linked immunoassay (ELISA) was used to measure the inflammation markers IL-6 in plasma and soluble (s)-CD14 in saliva. Flow cytometry was used to measure frequencies of activated CD4+, CD8+, and monocyte subsets in blood. Linear regression was used to assess the association between early ART and oral inflammation markers, and the association between oral inflammation and markers of systemic inflammation and immune activation. Results A total of 58 early-treated and 27 later-treated CLHIV were evaluated. The median duration on ART at oral assessment/saliva collection was 11 (interquartile range [IQR]10, 13) years. There was a trend for higher median sCD14 levels (p=0.063). BOP scores were also higher in the later-treated but not significantly so (p=0.2). In analyses, adjusted for age at oral health assessment and sex, pre-ART CD4 percentage <15% (coefficient = 0.145, p = 0.006), higher pre-ART HIV RNA level (coefficient = 0.028, p = 0.012), and initiating ART after 1 year (later-treated) (coefficient = 0.152, p= 0.015), were significantly associated with higher BOP score. None of the variables analyzed was associated with higher sCD14 level. Higher BOP scores were significantly associated with higher frequencies of activated CD4+ (coefficient = 0.351, p = 0.020), and activated CD8+ (coefficient = 0.579, p = 0.010) T cells, but were not associated with frequencies of intermediate, classical, or non-classical monocytes. sCD14 was not associated with frequencies of activated T cells nor any monocyte subset. Conclusion Later ART initiation, pre-ART immunosuppression, and higher pre-ART HIV RNA level were associated with more severe gingivitis after more than a decade of ART in CLHIV, and more severe gingivitis was associated with higher frequencies of activated T cells. Our findings suggest improving oral health in CLHIV may be a novel approach to addressing residual T cell activation in CLHIV on long-term ART.