Sleasman J W, Nelson R P, Goodenow M M, Wilfret D, Hutson A, Baseler M, Zuckerman J, Pizzo P A, Mueller B U
Department of Pediatrics and Department of Pathology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL, USA.
J Pediatr. 1999 May;134(5):597-606. doi: 10.1016/s0022-3476(99)70247-7.
To evaluate lymphocyte reconstitution after protease inhibitor therapy in children with human immunodeficiency virus (HIV) infection.
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.
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.
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.
评估蛋白酶抑制剂治疗对人类免疫缺陷病毒（HIV）感染儿童淋巴细胞重建的影响。
在一项I/II期临床试验中，对44名接受利托那韦单药治疗随后加用齐多夫定和去羟肌苷的HIV感染儿童进行了评估。该队列的中位年龄为6.8岁，疾病处于进展期（57%为美国疾病控制与预防中心C期，73%为免疫3期），且未接受过蛋白酶抑制剂治疗。
治疗4周后，CD4(+)和CD8(+) T细胞显著增加。CD4(+) T细胞持续增加，而CD8(+) T细胞在24周时恢复至基线水平。出乎意料的是，B细胞显著增加。CD4(+) T细胞亚群的变化显示，CD4(+) CD45RO T细胞最初增加，随后CD4(+) CD45RA T细胞持续增加。6岁以下儿童所有淋巴细胞群体的增加最为显著。即使在病毒载量恢复到治疗前水平的儿童中，也观察到CD4(+) T细胞计数有显著改善。
利托那韦治疗后淋巴细胞早期增加是再循环的结果，B细胞以及CD4(+) CD45RO和CD8(+) T细胞的增加表明了这一点。即使疾病处于进展期且病毒抑制不完全，儿童仍具有重建CD4(+) CD45RA T细胞的高潜力。
