Cellular immune responses in human immunodeficiency virus (HIV)‐1‐infected children: is immune restoration by highly active anti‐retroviral therapy comparable to non‐progression?

Summary The objective of this study was to investigate whether the restored immune functions of vertically human immunodeficiency virus (HIV)‐infected children who were severely immunodeficient before the initiation of highly active anti‐retroviral therapy (HAART) are comparable to those of untreated slow progressors. We therefore assessed T cell proliferation and cytokine [interferon (IFN)‐γ, interleukin (IL)‐5 and IL‐13] secretions after mitogen, recall antigens and HIV‐1‐specific stimulation in 12 untreated slow progressors, 16 untreated progressors and 18 treated patients. Treated children were profoundly immunodeficient before the initiation of HAART and had long‐lasting suppression of viral replication on treatment. We demonstrated that slow progressors are characterized not only by the preservation of HIV‐1‐specific lymphoproliferative responses but also by the fact that these responses are clearly T helper type 1 (Th1)‐polarized. Children on HAART had proliferative responses to HIV‐1 p24 antigen, purified protein derivative (PPD) and tetanus antigen similar to slow progressors and higher than those of progressors. However, in contrast to slow progressors, most treated children exhibited a release of Th2 cytokines accompanying the IFN‐γ secretion in response to the HIV‐1 p24 antigen. Moreover, despite higher proliferative responses to phytohaemagglutinin (PHA) than the two groups of untreated children, treated children had lower levels of IFN‐γ secretion in response to PHA than slow progressors. These data show that in severely immunodeficient vertically HIV‐infected children, a long‐lasting HAART allows recovering lymphoproliferative responses similar to untreated slow progressors. However, alterations in IFN‐γ secretion in response to the mitogen PHA persisted, and their cytokine release after HIV‐specific stimulation was biased towards a Th2 response.