Persistence of immune activation in lymphocytes of HIV-exposed noninfected newborns, children and adolescents.

Abstract

The use of antiretroviral therapy (ART) in pregnancy, peripartum and early life has reduced vertical transmission of HIV infection and has thus contributed to the increase in the number of vertically HIV exposed noninfected children (ENI). Although most children who were born to HIV-infected mothers and received antiretroviral therapy during pregnancy show no clinical symptoms, immunologic alterations have been described in newborns and infants, such as a reduced number of CD4+ T and B cells, a higher state of immune activation and alteration in the maturation of T lymphocytes. Recently, we found that ENI children and adolescents had higher apoptosis on B cells and reduced CD4+ T cell counts. Moreover, nucleoside reverse transcriptase inhibitors (NRTIs) to which children are exposed during pregnancy are known to produce mitochondrial toxicity. However, it is unclear whether these alterations persist into adulthood. Taken into consideration the clinical and laboratory abnormalities that have been observed in ENI children, we intend to evaluate the persistence of immune activation in lymphocytes of pediatric patients. Frozen samples from 60 ENI individuals in three age groups (cord blood, 12 months, 6-12 years) will be evaluated and compared with 65 healthy individuals age matched no ENI exposed, and 34 HIV-infected children and adolescents with 6 -12 years. Frozen cells will be marked for evaluation of immune activation (CD38, HLA-DR) in different subpopulations. The bacterial translocation will be evaluated through the quantification of plasma lipopolysaccharide (LPS) and soluble CD14. Plasma cytokine levels will be assessed to evaluate activation/inflammation. Lymphocyte turnover will be also evaluated through T-cell receptor excision circle (TREC) quantification. The results from this study may provide additional evidence that will support the follow-up and further investigation of these individuals.