Virological and Immunological Long-Term Outcome of Human Immunodeficiency Virus-1 Infected Children Treated before One Year and after Two Years of Age in a Resource-Limited Setting of South Africa

INTRODUCTION: Benefits of early Highly Active AntiRetroviral Therapy (HAART) to reduce infant mortality and morbidity have been demonstrated in resource-limited and rich settings. However, immunovirological data collected in Sub-Saharan Africa are scarce. This study describes the long-term outcome of South African children who started HAART before one year of age (Early Starters Cohort or ESC) and compare their immunovirological outcomes to children who started their therapy after two years of age (Late Starters Cohort or LSC). Immunovirological results will be compared in order to evaluate the long-term non-inferiority of early treatment initiation. METHODS: Fifty-five children were included in the ESC (mean follow-up period 7.9 years) and 96 children were included in the LSC (mean follow-up period 6.3 years). Children from the ESC and the LSC were subdivided into three subgroups according to CD4+% at HAART initiation (<15%, between 15-24% and ≥ 25%). RESULTS: All children included in the ESC achieved normal CD4% at least once during the entire follow-up period, contrary to the LSC where 89.6% children achieved normal CD4% (p=0.014). Furthermore, mean CD4+% became higher in the ESC six years after treatment initiation. Children with CD4+% between 15 and 24% at HAART initiation reached higher CD4+% in the ESC, three years after treatment initiation. The proportion of children who experienced virological failure (>100 cp/ml) was comparable in both cohorts but persistent undetectable viral load (<50 cp/ml) after initial virological suppression was more frequent in the ESC (p=0.008). Finally, the proportion of children with detectable viral loads (50 to 1000 cp/ml) at least one time during the entire follow-up period was higher in the LSC (p=0.0022). CONCLUSION: HAART appeared highly effective in terms of immunovirological outcomes both in children treated before one and after two years of age. The results of this study demonstrate that early treated children more often achieved normal CD4+%, tended to have higher mean CD4+% and more sustained virological suppression. These results encourage the current international recommendations to initiate HAART as soon as possible in RLS.