Association between age at antiretroviral therapy initiation and 24-month immune response in West-African HIV-infected children

Abstract

Objective: We describe the association between age at antiretroviral therapy (ART) initiation and 24-month CD4+ cell response in West African HIV-infected children. Methods: All HIV-infected children from the IeDEA paediatric West African cohort, initiating ART, with at least two CD4+ cell count measurements, including one at ART initiation (baseline) were included. CD4+ cell gain on ART was estimated using a multivariable linear mixed model adjusted for baseline variables: age, CD4+ cell count, sex, first-line ARTregimen. Kaplan-Meier survival curves and a Cox proportional hazards regression model compared immune recovery for age within 24 months post-ART. Results: Of the 4808 children initiated on ART, 3014 were enrolled at a median age of 5.6 years; 61.2% were immunodeficient. After 12 months, children at least 4 years at baseline had significantly lower CD4+ cell gains compared with children less than 2 years, the reference group (P<0.001). However, by 24 months, we observed higher CD4+ cell gain in children who initiated ART between 3 and 4 years compared with those less than 2 years (P<0.001). The 24-month CD4+ cell gain was also strongest in immunodeficient children at baseline. Among these children, 75% reached immune recovery: 12-month rates were significantly highest in all those aged 2-5 years at ART initiation compared with those less than 2 years. Beyond 12 months on ART, immune recovery was significantly lower in children initiated more than 5 years (adjusted hazard ratio: 0.69, 95% confidence interval: 0.56-0.86). Conclusion: These results suggest that both the initiation of ART at the earliest age less than 5 years and before any severe immunodeficiency is needed for improving 24-month immune recovery on ART.