Clinical and Immunologic Impact of CMV Coinfection Among Children Living With HIV in Canada

BACKGROUND: Although cytomegalovirus (CMV) disease has been well described among severely immunocompromised children living with HIV (CLWH), the impact of CMV coinfection, is not well understood. The objective of this study was to characterize the clinical and immunologic effects of CMV coinfection in CLWH in Canada. METHODS: This is a substudy of the Early Pediatric Initiation, Canada Child Cure Cohort study, which enrolled CLWH in Canada between 2014 and 2018. CMV serostatus was determined at the first (baseline) study visit, and HIV-1 viral load (VL), CMV VL, and lymphocyte subsets were quantified every 3-6 months. For a subset of participants, CD4 + and CD8 + T cell subsets were analyzed using flow cytometry. The clinical outcomes were recorded retrospectively at the baseline visit and prospectively during the study period. RESULTS: Of the 225 participants, 85.3% were CMV seropositive (CMV + ) and 81% had suppressed HIV VL. While there were no significant differences in clinical outcomes between CMV + and CMV - children, CMV + children had lower frequencies of CD4 + T cells, higher frequencies of CD8 + T cells, and lower CD4/CD8 ratio at baseline than CMV - children. Children with CMV + children also demonstrated a higher frequency of CD4 + effector memory cells, lower CD8 + naïve T cells, and higher frequencies of CD8 + terminally differentiated effector memory cells. These differences remained significant even after adjusting for HIV viral control. CONCLUSIONS: CMV coinfection is common among CLWH and is associated with distinct immunological changes despite the effective control of HIV replication with antiretroviral therapy. The long-term implications of these immunologic perturbations require further investigation.