Immunologic and virologic responses to HAART in severely immunocompromised HIV-1-infected children

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Abstract
To determine the long-term immunologic and virologic effects of highly active antiretroviral therapy (HAART) in children with AIDS. A prospective observational study. Two pediatric HIV clinics. Twenty-five protease-inhibitor naive HIV-infected children (aged 2-18 years) with advanced disease (CD4≤6%). HAART (one protease inhibitor and one or more nucleoside analogs). Diphtheria and tetanus immunization in six patients after 18 months of therapy. Changes in percentage of CD4 cells and plasma HIV-1 RNA levels; post-treatment assays of lymphoproliferative responses to recall antigens; CD4 cell memory phenotype. Median duration of follow-up was 18.8 months (range, 7.5-28 months). At baseline the CD4 cell percentage was 2% (range, 0-6%), this increased significantly to 16% (range, 3-48%) above baseline at 12 months (P=0.002). The mean maximum CD4 cell increase was 20.7% (range 4-48%) which corresponds to 657×106 cells/l (range, 30-2240×106 cells/l) above baseline. By contrast, the median viral load was not significantly lower at 12 months than at baseline (P=0.34), and only 25% of the patients had sustained undetectable viral load. Of the reconstituted CD4 cells 70% were naive, and none of the subjects had lymphoproliferative responses to tetanus and diphtheria although 40% did develop responses to Candida, an environmental antigen. A single immunization with diphtheria and tetanus toxoid produced lymphoproliferative responses to tetanus in three out of six patients. HAART was associated with sustained increases in CD4 cell counts, despite a high incidence of‚virologic failure‚. CD4 counts and the proportion of naive cells were higher than have been reported in adults, which may be a reflection of greater thymic activity in children. Memory cell clones for antigens encountered in the past which are not prevalent before therapy could not be expanded without additional antigenic exposure.