Reduced markers of HIV persistence and restricted HIV-specific immune responses after early antiretroviral therapy in children

Abstract

OBJECTIVE: Understanding the extent to which early antiretroviral therapy (ART) can limit the establishment and persistence of the HIV reservoir is an important step to designing interventions aimed at achieving HIV cure. We measured the markers of HIV persistence and HIV-specific immunity in early treated children. DESIGN: This is a cross-sectional study that enrolled 15 children older than 2 years of age who initiated ART before 6 months of age and had sustained viral suppression. Total and integrated HIV DNA, and 2-LTR circles in CD4 T cells, HIV antibody response by fourth generation HIV enzyme immunoassay, and CD4 and CD8 T-cell responses to gag/env peptides by intracellular cytokine staining of CD4 and CD8 T cells were measured. RESULTS: The median current age was 6.3 years and age at ART initiation was 17 weeks. The median duration of viral suppression was 6 years, and all had HIV RNA less than 50 copies/ml. The median CD4 T cells was 44%. The median total HIV DNA was 132 copies/10 CD4 T cells (range 11-1804) and integrated HIV DNA was 17 copies/10 CD4 T cells (range 0-516), and no one had detectable 2-LTR circles. Nine of the 15 children (60%) had undetectable or extremely low integrated HIV DNA (<20 copies/10 CD4 T cells). All except one (93%) had undetectable HIV-specific CD4/CD8 cell responses and seven (47%) had nonreactive enzyme immunoassay. CONCLUSION: Early ART resulted in very low levels of markers of HIV persistence and undetectable HIV-specific immune responses in the majority of HIV-infected children who started ART before 6 months of age.