Protease inhibitor and triple-drug therapy: cellular immune parameters are not restored in pediatric AIDS patients after 6 months of treatment.
OBJECTIVE
To assess whether treatment of HIV-positive children by antiretroviral drugs for a 6-month period would improve immune function significantly.


METHODS
Immunological assessment of 89 HIV-positive children who received protease inhibitor monotherapy for 12-16 weeks as part of phase I/II studies, followed by triple antiretroviral therapy for an additional 12 weeks, was conducted. Immunological parameters were assessed in vitro at four time points (at enrollment, at weeks 2-4, at weeks 12-16, and at weeks 24-28). Assessments included: cytokine production by monocytes, T-cell proliferation to mitogen or recall antigens (including an HIV antigen) and apoptotic cell death. Plasma levels of tumor necrosis factor (TNF)-alpha and soluble TNF receptor (sTNF-R) were also measured, in addition to CD4+ T-lymphocyte counts and viral load. In addition, limited analyses were performed on samples from 17 children after 120 weeks of therapy, including 104 weeks of triple therapy.


RESULTS
At enrollment, the 89 children exhibited severe immune defects. Antiretroviral therapy raised CD4+ T-lymphocyte counts significantly and decreased viral loads. In contrast, the in vitro immune parameters studied were not improved, except for plasma levels of sTNF-RII which decreased in parallel with the decrease in viral load. In addition, there was a trend towards increased skin test reactivity for the ritonavir-treated children. No differences were seen in the immune parameters whether the patients were treated with mono- or triple therapy. Results obtained after 120 weeks of therapy demonstrated that defective interleukin-12 production was not restored by long-term therapy.


CONCLUSIONS
After 6 months of therapy, with the exception of decreased sTNF-RII levels, and a trend towards increased skin test reactivity, restoration of several defective cellular immune responses did not occur despite significantly decreased viral loads and increased CD4+ T-lymphocyte counts.
Chougnet
C
C
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Fowke
K R
KR
Mueller
B U
BU
Smith
S
S
Zuckerman
J
J
Jankelevitch
S
S
Steinberg
S M
SM
Luban
N
N
Pizzo
P A
PA
Shearer
G M
GM
D000293:Adolescent; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D017209:Apoptosis; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006801:Humans; D007111:Immunity, Cellular; D019469:Indinavir / Q000627:therapeutic use; D007223:Infant; D008213:Lymphocyte Activation; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D019438:Ritonavir / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D019562:Viral Load
D019380:Anti-HIV Agents; D016207:Cytokines; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D019469:Indinavir; D019438:Ritonavir