Immunoreconstitution after ritonavir therapy in children with human immunodeficiency virus infection involves multiple lymphocyte lineages

Objective: To evaluate lymphocyte reconstitution after protease inhibitor t herapy in children with human immunodeficiency virus (HIV) infection. Study design: Forty-four HIV-infected children receiving ritonavir monother apy followed by the addition of zidovudine and didanosine were evaluated du ring 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 signif icant increase in B cells. Changes in CD4(+) T-cell subsets revealed an ini tial 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 count s was observed even in those children whose viral burden returned to prethe rapy levels. Conclusions: Early increases in lymphocytes after ritonavir therapy are a r esult 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 suppress ion.