CD4R cell count recovery following initiation of HIV antiretroviral therapy in older childhood and adolescence

Abstract

Objective: To investigate CD4 cell count recovery following ART initiation in perinatally HIV-infected children diagnosed in later childhood. Design: Observational prospective cohort study of newly diagnosed children aged 6 15 in Harare, Zimbabwe. Methods: Participants were enrolled into a cohort at seven primary healthcare clinics between January 2013 and January 2015. ART was initiated according to national guidelines and CD4 cell counts were performed 6-monthly over 18 months. The relationship between CD4 cell count and time on ART was investigated using regression analysis with fixed (population) and random (individual) effects, and age at ART initiation as a covariate. Results: Of the 307 participants who initiated ART, the median age at initiation was 11.7 years (interquartile range 9.6 13.8). The addition of an individual intercept and slope as random effects significantly improved the model fit compared with a fixed effects-only model. CD4 response (using a square-root transformation) was best modelled using a two-knot linear spline, with significant effects of time on ART and age at ART initiation. Younger children had a higher CD4 cell count at ART initiation (17.9 cells/ml per year of age), an accelerated increase during the first 3 months on ART (38.9 cells/ml per year of age at day 84), and a sustained higher CD4 cell count. Conclusion: Earlier ART initiation in older children is associated with accelerated CD4 cell count recovery and lasting immune reconstitution. Our findings support WHO guidance recommending ART initiation in all children, irrespective of disease stage and CD4 cell count.