Sm. Essajee et al., Immunologic and virologic responses to HAART in severely immunocompromisedHIV-1-infected children, AIDS, 13(18), 1999, pp. 2523-2532
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 clini
cs.
Participants: Twenty-five protease-inhibitor naive HIV-infected children (a
ged 2-18 years) with advanced disease (CD4 less than or equal to 6%).
Intervention: HAART tone protease inhibitor and one or more nucleoside anal
ogs). Diphtheria and tetanus immunization in six patients after 18 months o
f therapy.
Main outcome measures: Changes in percentage of CD4 cells and plasma HIV-1
RNA levels; post-treatment assays of lymphoproliferative responses to recal
l 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 corresp
onds to 657 x 10(6) cells/l (range, 30-2240 x 10(6) cells/l) above baseline
. By contrast, the median viral load was not significantly lower at 12 mont
hs 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 diph
theria although 40% did develop responses to Candida, an environmental anti
gen. A single immunization with diphtheria and tetanus toroid produced lymp
hoproliferative responses to tetanus in th ree out of six patients.
Conclusions: HAART was associated with sustained increases in CD4 cell coun
ts, despite a high incidence of 'virologic failure'. CD4 counts and the pro
portion of naive cells were higher than have been reported in adults, which
may be a reflection of greater thymic activity in children. Memory cell cl
ones for antigens encountered in the past which are not prevalent before th
erapy could not be expanded without additional antigenic exposure. (C) 1999
Lippincott Williams & Wilkins.