Highly Active Antiretroviral Therapy in Human Immunodeficiency Virus Type 1-Infected Children: Analysis of Cellular Immune Responses

Abstract

ABSTRACT The present study analyzes the effect of highly active antiretroviral therapy (HAART) on restoration of cellular immunity in human immunodeficiency virus (HIV)-infected children over a 24-week period following initiation of HAART with ritonavir, nevirapine, and stavudine. The immunological parameters evaluated at four time points (at enrollment and at 4, 12, and 24 weeks of therapy) included cytokine production by monocytes as well as T-cell proliferation in response to mitogen, alloantigen, and recall antigens including HIV type 1 envelope peptides. Circulating levels of interleukin-16 (IL-16) were measured, in addition to CD4 + T-cell counts, plasma HIV RNA levels, and the delayed-type hypersensitivity (DTH) response. At enrollment the children exhibited defects in several immune parameters measured. Therapy increased CD4 + T-cell counts and decreased viral loads significantly. By contrast, the only immunological parameter that was significantly increased was IL-12 p70 production by monocytes; the DTH response to Candida albicans also showed a strong increase in patients becoming positive. In conclusion, these results demonstrate that HAART in HIV-infected children affects the dynamics of HIV replication and the CD4 + T-cell count over 24 weeks, similar to the pattern seen in HIV-infected adults. Furthermore, these data indicate improvement in antigen-presenting cell immunological function in HIV-infected children induced by HAART.