AIDS. 2010 Jan 16;24(2):231-41. doi: 10.1097/QAD.0b013e328333d343.
To evaluate clinical, immunological and virological consequences of CD4-guided antiretroviral therapy (ART) planned treatment interruptions (PTIs) compared with continuous therapy in children with chronic HIV infection in the Paediatric European Network for Treatment of AIDS 11 trial.
This was a multicentre, 72-week, open, randomized, phase II trial.
One hundred and nine children with HIV-RNA below 50 copies/ml and CD4% of at least 30% (2-6 years) or at least 25% and CD4 cell count of at least 500 cells/microl (7-15 years) were randomized to continuous therapy (53) or PTI (56). In PTI, ART was restarted if confirmed CD4% was less than 20% or more than 48 weeks had been spent off ART. The primary outcome was Centers for Disease Control and Prevention (CDC) stage C event, death or CD4% less than 15% (and CD4 cell count less than 200 cells/microl for children aged 7-15 years).
At baseline, median (interquartile range) age was 9 (6-12) years, CD4% 37% (33-41), CD4 cell count 966 (793-1258) cells/microl, nadir CD4% before combination ART 18% (10-27), time on ART 6 (3-6) years and 26% were CDC stage C. After median (range) 130 (33-180) weeks of follow-up, 4 versus 48% of time was spent off ART in continuous therapy and PTI, respectively. No child died or had a new CDC stage C event; one (2%) continuous therapy versus four (7%) PTI children had a primary outcome based on CD4%/cell count (P = 0.2). Lower nadir CD4% predicted faster CD4% decline after stopping ART. Younger age and higher nadir CD4% predicted being off ART for at least 48 weeks and better CD4% recovery following PTI.
In this first paediatric trial of PTI, there were no serious clinical outcomes. Younger children had better CD4% recovery after PTIs. Immunology substudies and long-term follow-up in Paediatric European Network for Treatment of AIDS 11 trial are ongoing. Further research into the role of treatment interruption in children is required, particularly, as guidelines now recommend early ART for all infected infants.
评估在 Paediatric European Network for Treatment of AIDS 11 试验中，CD4 指导的抗逆转录病毒治疗（ART）计划治疗中断（PTI）与连续治疗相比对慢性 HIV 感染儿童的临床、免疫和病毒学后果的影响。
这是一项多中心、72 周、开放、随机、二期试验。
109 名 HIV-RNA 低于 50 拷贝/ml 且 CD4%至少为 30%（2-6 岁）或至少为 25%且 CD4 细胞计数至少为 500 个细胞/μl（7-15 岁）的儿童被随机分为连续治疗组（53 名）或 PTI 组（56 名）。在 PTI 中，如果确认 CD4%低于 20%或已停止 ART 超过 48 周，则重新开始 ART。主要结局是疾病控制和预防中心（CDC）C 期事件、死亡或 CD4%低于 15%（7-15 岁儿童的 CD4 细胞计数低于 200 个细胞/μl）。
在基线时，中位（四分位距）年龄为 9 岁（6-12 岁），CD4%为 37%（33-41），CD4 细胞计数为 966 个细胞/μl（793-1258），开始联合 ART 前的最低 CD4%为 18%（10-27），ART 时间为 6（3-6）年，26%为 CDC C 期。在中位（范围）130 周（33-180 周）的随访后，连续治疗组和 PTI 组分别有 4%和 48%的时间停止 ART。没有儿童死亡或出现新的 CDC C 期事件；1 名（2%）连续治疗组和 4 名（7%）PTI 组的主要结局基于 CD4%/细胞计数（P=0.2）。较低的最低 CD4%预示着停止 ART 后 CD4%下降更快。年龄较小和最低 CD4%较高预示着至少停止 ART 48 周和 PTI 后更好的 CD4%恢复。
在这项针对儿童的首次 PTI 试验中，没有发生严重的临床结局。年龄较小的儿童在 PTI 后 CD4%恢复更好。儿科艾滋病治疗网络 11 试验的免疫亚研究和长期随访正在进行中。需要进一步研究儿童治疗中断的作用，特别是因为现在的指南建议所有感染婴儿都应尽早开始 ART。
