Immunoreconstitution after ritonavir therapy in children with human immunodeficiency virus infection involves multiple lymphocyte lineages.
OBJECTIVE
To evaluate lymphocyte reconstitution after protease inhibitor therapy in children with human immunodeficiency virus (HIV) infection.


METHODS
Forty-four HIV-infected children receiving ritonavir monotherapy followed by the addition of zidovudine and didanosine were evaluated during a phase I/II clinical trial. The cohort had a median age of 6.8 years and advanced disease (57% Centers for Disease Control and Prevention stage C, 73% immune stage 3) and was naive to protease inhibitor therapy.


RESULTS
After 4 weeks of therapy, there was a significant increase in CD4(+) and CD8(+) T cells. CD4(+) T cells continued to increase, whereas CD8(+) T cells returned to baseline by 24 weeks. Unexpectedly, there was a significant increase in B cells. Changes in CD4(+) T-cell subsets revealed an initial increase in CD4(+) CD45RO T cells followed by a sustained increase in CD4(+) CD45RA T cells. Children <6 years of age had the highest increase in all lymphocyte populations. Significant improvement in CD4(+) T-cell counts was observed even in those children whose viral burden returned to pre-therapy levels.


CONCLUSIONS
Early increases in lymphocytes after ritonavir therapy are a result of recirculation, as shown by increases in B cells and CD4(+) CD45RO and CD8(+) T cells. Children exhibited a high potential to reconstitute CD4(+) CD45RA T cells even with advanced disease and incomplete viral suppression.
Sleasman
J W
JW
Department of Pediatrics and Department of Pathology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL, USA.
Nelson
R P
RP
Goodenow
M M
MM
Wilfret
D
D
Hutson
A
A
Baseler
M
M
Zuckerman
J
J
Pizzo
P A
PA
Mueller
B U
BU
D000293:Adolescent; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes; D002648:Child; D002675:Child, Preschool; D016049:Didanosine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D017493:Leukocyte Common Antigens; D016131:Lymphocyte Subsets; D019438:Ritonavir / Q000627:therapeutic use*; D019562:Viral Load; D015215:Zidovudine / Q000627:therapeutic use
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D015215:Zidovudine; D017493:Leukocyte Common Antigens; D016049:Didanosine; D019438:Ritonavir