Objective To evaluate the effects of antiretroviral treatment (ART) for mother-to-child transmission of HIV and infant/maternal characteristics on total lymphocytes (TLC) and lymphocyte subsets in uninfected children of HIV-1-infected mothers. Design The European Collaborative Study followed 1663 uninfected children from birth until at least 8 years of age using a standard protocol. Methods Smoothers (running medians) illustrated patterns of immune markers over age by ART exposure and race. Associations between lymphocyte parameters and maternal/infant characteristics were quantified in linear regression analyses using z-scores obtained after modelling log10-transformed TLC, CD4 and CD8 cell counts using the LMS method. Cox proportional hazard models assessed time to TLC, CD4 and CD8 cell counts below the defined cut-off. Covariates included prematurity, gender, race, drug withdrawal and ART exposure. Results Overall, black children had lower TLC, CD4 and CD8 cell counts than white children, and an increased risk of TLC, CD4 and CD8 cell counts below the cut-off. ART exposure was associated with TLC levels (but not with TLC below the cut-off for lymphopenia), with reduced CD4 cell counts in the first year of life, and with reduced CD8 cell counts until at least 8 years of age. Duration and intensity of ART exposure was associated with TLC levels. Conclusion The effect of ART exposure in fetal and early life on TLC and CD8 cell counts was prolonged until at least 8 years. These results add to the growing list of adverse effects associated with ART used as prevention of mother-to-child transmission of HIV.

Maternal and infant factors and lymphocyte, CD4 and CD8 cell counts in uninfected children of HIV-1-infected mothers.

Background: Racial immuno-haematological differences have been reported in children but to date have not been well quantified. Aim: To investigate differences in haemato-immunological markers over age between children born and living in Europe and Uganda. Subjects: HIV-uninfected children living in Uganda (n=1633) with cross-sectional data. Black (n=604) and white children (n=1355) living in Europe, both with prospective data. The children born in Europe were HIV-uninfected but born to HIV-infected mothers and were included in the European Collaborative Study (ECS). Methods: Patterns and levels of total lymphocyte (TLC), CD4+, CD8+ counts and CD4% were visualised by smoothers (a line representing the weighted average of all measurements over age by study group). Differences between groups were quantified using age-standardised Z-scores for individual TLC, CD4+ and CD8+ counts in uni- and multivariate regression models. Results: In infancy, TLC, CD4+ and CD8+ counts were lower in Ugandan than blac...

Within and between race differences in lymphocyte, CD4+, CD8+ and neutrophil levels in HIV-uninfected children with or without HIV exposure in Europe and Uganda

The monocyte-macrophage lineage represents a primitive first line of defense, maintained and refined in evolution. In higher organisms, while retaining their basic role of primary line of resistance, phagocytic cells have become integrated into the subsequently evolved mechanisms of specific immunity. Cooperation between lymphoid cells and macrophages occurs at different levels in the genesis of immune responses, and, in inflammatory sites, they play important roles in the expression of cell-mediated immune reactions. The role played by mononuclear phagocytes in resistance against infectious agents has long been recognized. Age-dependent resistance to infectious agents is a well-known phenomenon and host responses to a range of microorganisms, including bacteria, mycobacteria, yeasts, parasites, and viruses are relatively poor in the perinatal period in humans (Weston et al. 1977; Bellanti and Hurtado 1976). Considerable evidence has accumulated that selected functions of mononuclear phagocytes are defective in newborns and that this defect of the mononuclear phagocyte system plays a crucial role in increased susceptibility to some infectious agents (Pitt et al. 1977). In this review we will concisely discuss selected aspects of mononuclear phagocyte function in the perinatal period, emphasizing the selectivity of alterations. Some recent results on the immunobiology of placental and breast milk macrophages will also be mentioned, since, in addition to having attracted our attention, they have an obvious bearing on resistance in the perinatal period.

Gotoff Sp

Papers

Immunologic disorders in children.