Status: Funded - Open
Anthony Hsieh, PhD
BACKGROUND: Over 90% of children living with HIV are in sub-Saharan Africa, and the prevalence of cytomegalovirus (CMV) coinfection in this population is nearly ubiquitous. Children coinfected with perinatally-acquired CMV and HIV are susceptible to comorbidities such as impaired physical development and stunted growth, pneumonia and chronic lung disease, as well as neurological diseases, likely because of the cumulative immune burden imposed by the two viruses. GAP: HIV disease progression and poor viral control are clearly suspected drivers of these comorbidities, and there is accumulating evidence to suggest that active CMV replication may have a similar effect. However, it remains unknown whether CMV replication is associated with indicators of increased immune burden, such as accelerated immune aging. HYPOTHESIS: I hypothesize that CMV replication, as measured by the frequency and severity of CMV reactivations, is associated with immune biomarkers consistent with older age, including shorter telomere length and more differentiated CD8+ T cells. METHODS: Approximately 100 Zimbabwean children aged 8-16 will be invited to join a sub-study from a larger cohort of 600 participants. Blood collection will occur weekly for 4 weeks, then monthly for 5 months to measure CMV replication dynamics, following which immune aging markers will be characterized. RESULTS: Pending. IMPACT: If immune aging markers are associated with CMV replication, then it would inform a clinical trial to determine whether controlling viremia using antiretroviral therapy in children with perinatal CMV can abrogate impaired physical development and other comorbidities.