Immunologic and virologic responses to HAART in severely immunocompromised HIV-1-infected children.
OBJECTIVE
To determine the long-term immunologic and virologic effects of highly active antiretroviral therapy (HAART) in children with AIDS.


METHODS
A prospective observational study.


METHODS
Two pediatric HIV clinics.


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


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


METHODS
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.
Essajee
S M
SM
Department of Pediatrics, New York University Medical Center/Bellevue Hospital, New York 10016, USA.
Kim
M
M
Gonzalez
C
C
Rigaud
M
M
Kaul
A
A
Chandwani
S
S
Hoover
W
W
Lawrence
R
R
Spiegel
H
H
Pollack
H
H
Krasinski
K
K
Borkowsky
W
W
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000628:therapy / Q000821:virology*; D000293:Adolescent; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D001428:Bacterial Vaccines / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D003627:Data Interpretation, Statistical; D004359:Drug Therapy, Combination; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1; D006801:Humans; D011446:Prospective Studies; D019562:Viral Load
D019380:Anti-HIV Agents; D001428:Bacterial Vaccines; D017320:HIV Protease Inhibitors