Dissecting the humoral antibody specificity in relation to virus evolution in pediatric HIV infection

Worldwide there more than 30 million people living with HIV: 2,5 million are children under 15 years of age who mainly acquired the infection through mother to child transmission (MTCT); 90% of these children lives in Sub Saharan Africa. Transmission can occur during pregnancy (15-20%), at delivery (45-55%) or via breastfeeding (30-35%). maternal RNA levels, CD4+T cells count, mode of delivery and gestional age have been associated with MTCT. HIV-1 infected children display different pattern of clinical evolution with fast progressors, delayed progressors and long term non progressors. This different clinical evolution could be determined by the interaction of virological, cellular and immunological factors already established at birth. The fact that during the first month of life the viral RNA load in plasma and proviral DNA in PBMC of the newborn rise up to levels which are higher than those observed in adults supports thei dea that the newborn immune system is not able to contain virus replication. Despite this enormous viral burden it appears that evident genotypic variation of the HIV quasispecies appears only after 6 months of age, i.e. when an immune response has established. It has been observed that the increase in length and glycosylation of the gp120 env is a response to the neutralizing antibody response in infected adults and may serve as an escape mechanism. Emergence of virus variants in children resistant to neutralization by autologous sera has been described in a few reports but lacks a clear association with progressive HIV-1 disease. So far, the humoral immune response in mother or in children has never shown a clear correlation with the infection event.