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AIDS. 1999 Dec 24;13(18):2523-32.

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

Author information

1
Department of Pediatrics, New York University Medical Center/Bellevue Hospital, New York 10016, USA.

Abstract

OBJECTIVE:

To determine the long-term immunologic and virologic effects of highly active antiretroviral therapy (HAART) in children with AIDS.

DESIGN:

A prospective observational study.

SETTING:

Two pediatric HIV clinics.

PARTICIPANTS:

Twenty-five protease-inhibitor naive HIV-infected children (aged 2-18 years) with advanced disease (CD4 < or =6%).

INTERVENTION:

HAART (one protease inhibitor and one or more nucleoside analogs). Diphtheria and tetanus immunization in six patients after 18 months of therapy.

MAIN OUTCOME MEASURES:

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.

RESULTS:

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 657x10(6) cells/l (range, 30-2240x10(6) 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.

CONCLUSIONS:

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.

[Indexed for MEDLINE]

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