Project Details

Establishing the association between cytomegalovirus viremia and immune aging in Zimbabwean children

Anthony Hsieh, PhD

Summary

BACKGROUND: Over 90% of children with HIV are in sub-Saharan Africa, where the prevalence of cytomegalovirus (CMV) coinfection is ubiquitous. Children coinfected with perinatally-acquired CMV/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: CMV replication is associated with immune biomarkers consistent with older age, including shorter telomere length and more differentiated CD8+ T cells. METHODS: CMV IgG and DNA levels will be measured in 558 Zimbabwean children aged 8-16. PBMC telomere length will be measured using qPCR, and DNA methylation arrays will be used to quantify T cell differentiation and epigenetic age. RESULTS: Among HIV+ participants, relative CMV IgG levels were 26.71±6.01 (average±SD) compared to 23.33±5.29 among controls (p<0.001). CMV viremia >100 IU/ml was detected in 32 participants (5.7%). This was higher among HIV+ participants (7.7%) than controls (3.8%, p=0.047). Further 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.