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. Study design: 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 pretherapy 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.