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 ART regimen. 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 enrol led 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.

Effect of Age at Antiretroviral Therapy Initiation on Catch-up Growth Within the First 24 Months Among HIV-infected Children in the IeDEA West African Pediatric Cohort

“…Thus, after ART initiation, immune system disorders can be reversed and associated nutritional problems can be reduced. We report elsewhere in the same population that the initiation of ART at the earliest age before 5 years and before any severe immunodeficiency occurred is needed to optimize the 24-month immune recovery on ART [37]. …”

Missed opportunities of inclusion in a cohort of HIV‐infected children to initiate antiretroviral treatment before the age of two in West Africa, 2011 to 2013

“…Consequently, providing a continuum of care for HIV-exposed children remains challenging. Those HIV-infected children who have a chance to access ART are frequently treated late, at an advanced age (median age greater than five years) and at an advanced stage of the disease [ 13 , 14 ].…”

Immune activation despite preserved CD4 T cells in perinatally HIV-infected children and adolescents

“…Adult studies suggest ART must be started within 12 months of seroconversion to restore immunologic health [ 44 ] and early ART initiation might contribute to more rapid and robust CD4:CD8 ratio normalization [ 29 ]. In children, one report demonstrated that starting ART before 5 years of age results in stronger CD4 T cell gains but not normalization within 24 months of treatment [ 34 ]. A statistical model developed to estimate long-term CD4 recovery, demonstrated that ART should be initiated when CD4-for-age is high, even if there is a low risk of immediate disease progression to maximize CD4 reconstitution in children older than 10 years [ 45 ].…”