Divergent populations of HIV-infected naive and memory CD4+ T cell clones in children on antiretroviral therapy.
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BACKGROUNDNaive cells comprise 90% of the CD4+ T cell population in neonates and exhibit distinct age-specific capacities for proliferation and activation. We hypothesized that HIV-infected naive CD4+ T cell populations in children on long-term antiretroviral therapy (ART) would thus be distinct from infected memory cells.METHODSPeripheral blood naive and memory CD4+ T cells from 8 children with perinatal HIV on ART initiated at age 1.7-17 months were isolated by FACS. DNA was extracted from sorted cells, and HIV proviruses were counted, evaluated for intactness, and subjected to integration site analysis (ISA).RESULTSNaive CD4+ T cells containing HIV proviruses were detected in children with 95% statistical confidence. A median 4.7% of long terminal repeat-containing naive CD4+ T cells also contained HIV genetic elements consistent with intactness. Full-length proviral sequencing confirmed intactness of 1 provirus. In the participant with the greatest degree of naive cell infection, ISA revealed infected expanded cell clones in both naive and memory T cells, with no common HIV integration sites detected between subsets. Divergent integration site profiles reflected differential gene expression patterns of naive and memory T cells.CONCLUSIONThese results demonstrate that HIV persisted in both naive and memory CD4+ T cells that underwent clonal expansion and harbored intact proviruses, and suggest that infected memory T cell clones do not frequently arise from naive cell differentiation in children with perinatal HIV on long-term ART.FUNDINGCenter for Cancer Research, NCI; Office of AIDS Research; NCI FLEX; Children's and Emory Junior Faculty Focused Award.