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Immunologic and virologic responses to HAART in severely immunocompromised HIV-1-infected children
S M Essajee1, M Kim, C Gonzalez
1Department of Pediatrics, New York University Medical Center/Bellevue Hospital, New York 10016, USA.
Insights
Highly active antiretroviral therapy (HAART) significantly increased CD4 cell counts in children with AIDS, despite challenges in viral load suppression. Immune reconstitution primarily involved naive T-cells, suggesting potential for greater thymic activity in pediatric patients.
Area of Science:
- Pediatric Immunology
- Virology
- HIV/AIDS Research
Background:
- Children with advanced HIV/AIDS often have compromised immune systems.
- Highly Active Antiretroviral Therapy (HAART) is a standard treatment for HIV.
- Long-term effects of HAART on pediatric immune reconstitution require further investigation.
Purpose of the Study:
- To evaluate the long-term immunologic and virologic outcomes of HAART in children with Acquired Immunodeficiency Syndrome (AIDS).
- To assess changes in CD4 cell counts, viral load, and immune responses after HAART initiation.
Main Methods:
- A prospective observational study was conducted in two pediatric HIV clinics.
- Twenty-five protease-inhibitor naive HIV-infected children (aged 2-18 years) with advanced disease (CD4 ≤ 6%) received HAART.
- Changes in CD4 cell percentage, plasma HIV-1 RNA levels, lymphoproliferative responses, and CD4 cell phenotype were monitored.
Main Results:
- HAART led to a significant increase in CD4 cell percentage (from 2% to 16% at 12 months).
- The majority of reconstituted CD4 cells were naive (70%), and viral load suppression was achieved in only 25% of patients.
- Lymphoproliferative responses to tetanus and diphtheria were absent initially, but some responses to Candida were observed.
Conclusions:
- HAART is associated with sustained increases in CD4 cell counts in children, even with virologic failure.
- Higher CD4 counts and a greater proportion of naive cells in children compared to adults may indicate enhanced thymic activity.
- Expansion of memory cell clones for previously encountered antigens requires additional antigenic stimulation.
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.
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