Persistent immunological repercussions of late antiretroviral initiation in children with HIV

OBJECTIVE: We aimed to evaluate how age at antiretroviral treatment (ART) initiation modified immune parameters and vaccine responses in a Brazilian cohort of children with perinatally acquired HIV on long-term treatment. DESIGN: Cross-sectional study including children <18 years; ART for ≥6 months; and HIV viral load <50 copies/ml. METHODS: Data was abstracted from medical charts and blood was collected for serology and PBMC isolation. Antibody titers for hepatitis A and B, rubella, mumps and measles were measured. T cells with markers for senescence (CD57 + ), anergy (CD28 - ), apoptosis (CD95 + ), activation (CD38 + , CCR5 + , HLA-DR + ) and exhaustion (PD-1 + ) were analyzed by flow cytometry. Children were categorized in four groups: ART initiation <6 months; ≥6 months <1 year; ≥1 year <5 years; ≥5 years. RESULTS: Fifty-five participants with a median age of 12 (8.3;15.9) years and median time on ART of 9 (5.0;13.2) years were included. Median age at ART initiation was 1.8 (0.6;3.6) years. Compared to those starting ART later, children who initiated ART earlier (<1 year of age, and especially < 6 months) had higher CD4 + counts, CD4 + nadir, and CD4 + /CD8 + ratio. Earlier ART was associated with CD4 + and CD8 + profiles with lower frequencies of activation, senescence, and exhaustion markers, and higher antibody titers for mumps, measles and rubella. Activation, senescence, and exhaustion markers correlated with poorer vaccine response. CONCLUSION: Children who started ART later in life presented with worse immune outcomes even after long-term ART.