Luzuriaga Katherine, McManus Margaret, Mofenson Lynne, Britto Paula, Graham Bobbie, Sullivan John L
Department of Pediatrics and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Mass 01605, USA.
N Engl J Med. 2004 Jun 10;350(24):2471-80. doi: 10.1056/NEJMoa032706.
Depletion of CD4 T-cell counts or progression of human immunodeficiency virus (HIV) disease occurs rapidly in children, but few data address the efficacy of aggressive therapy for HIV-infected children.
We evaluated the safety, tolerability, and activity of three regimens of antiretroviral therapy in a multicenter, open-label, phase 1-2 trial. Children infected with HIV type 1 (HIV-1) were stratified at entry according to age--three months or younger (early therapy) or older than three months (delayed therapy)--and assigned sequentially to one of three regimens. Children continued to receive treatment for up to 200 weeks if the plasma HIV-1 RNA level was less than 1000 copies per milliliter by 16 weeks.
Plasma HIV-1 RNA levels fell from a median of 5.3 log copies per milliliter (range, 3.3 to 6.4 log copies per milliliter) at baseline to less than 1000 copies per milliliter at 16 weeks in 32 of 52 infants (62 percent). Plasma HIV-1 RNA levels were below 400 copies per milliliter at 48 weeks in 26 infants (50 percent) and at 200 weeks in 23 infants (44 percent). An intention-to-treat analysis revealed that significantly more children who received stavudine, lamivudine, nevirapine, and nelfinavir had plasma HIV-1 RNA levels of less than 400 copies per milliliter at 48 weeks (83 percent) and 200 weeks (72 percent) than children who received reverse-transcriptase inhibitors alone (P=0.001 and P=0.01, respectively). Fewer infants in the delayed-therapy group than in the early-therapy group (30 percent vs. 60 percent) had plasma HIV-1 RNA levels of less than 400 copies per milliliter at 200 weeks (P=0.03). Treatment-associated adverse effects were infrequent.
In this phase 1-2 trial involving HIV-1-infected children, an age of three months or younger at the initiation of therapy and treatment with stavudine, lamivudine, nevirapine, and nelfinavir were associated with improved long-term viral suppression. Larger, randomized trials are required to define the optimal time to initiate therapy and the optimal regimen for these infants.
儿童中，CD4 T细胞计数的减少或人类免疫缺陷病毒（HIV）疾病的进展迅速，但针对HIV感染儿童的积极治疗效果的数据较少。
在一项多中心、开放标签的1-2期试验中，我们评估了三种抗逆转录病毒治疗方案的安全性、耐受性和活性。感染1型HIV（HIV-1）的儿童在入组时根据年龄分层——三个月及以下（早期治疗）或三个月以上（延迟治疗）——并依次分配到三种方案之一。如果血浆HIV-1 RNA水平在16周时低于每毫升1000拷贝，则儿童继续接受治疗长达200周。
52名婴儿中的32名（62%）血浆HIV-1 RNA水平从基线时的中位数每毫升5.3 log拷贝（范围为每毫升3.3至6.4 log拷贝）降至16周时的每毫升低于1000拷贝。26名婴儿（50%）在48周时血浆HIV-1 RNA水平低于每毫升400拷贝，23名婴儿（44%）在200周时低于该水平。意向性分析显示，接受司他夫定、拉米夫定、奈韦拉平和奈非那韦治疗的儿童在48周（83%）和200周（72%）时血浆HIV-1 RNA水平低于每毫升400拷贝的比例显著高于仅接受逆转录酶抑制剂治疗的儿童（分别为P = 0.001和P = 0.01）。延迟治疗组中在200周时血浆HIV-1 RNA水平低于每毫升400拷贝的婴儿少于早期治疗组（30%对60%）（P = 0.03）。与治疗相关的不良反应很少见。
在这项涉及HIV-1感染儿童的1-2期试验中，治疗开始时年龄在三个月及以下以及使用司他夫定、拉米夫定、奈韦拉平和奈非那韦治疗与长期病毒抑制改善相关。需要进行更大规模的随机试验来确定这些婴儿开始治疗的最佳时间和最佳方案。
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