Early antiretroviral therapy and mortality among HIV-infected infants.
Early antiretroviral therapy and mortality among HIV-infected infants.
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DOI：
10.1056/nejmoa0800971
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发表时间：
2008-11-20
期刊：
影响因子：
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通讯作者：
CHER Study Team
中科院分区：
文献类型：
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作者：
Violari A;Cotton MF;Gibb DM;Babiker AG;Steyn J;Madhi SA;Jean-Philippe P;McIntyre JA;CHER Study Team
在1型人体免疫机能丧失病毒（HIV-1）血清阳性率高的国家，艾滋病毒感染是婴儿死亡率的主要原因。我们调查了HIV感染儿童早期抗逆转录病毒治疗（CHER）试验中的抗逆转录病毒治疗策略。6至12周大的艾滋病毒感染婴儿，CD 4淋巴细胞百分比（CD 4百分比）25%或以上的患者被随机分配接受抗逆转录病毒治疗（洛匹那韦-利托那韦，齐多夫定，和拉米夫定），当CD 4百分比下降到20%以下时（或如果孩子小于1岁，则为25%）或符合临床标准（延迟抗逆转录病毒治疗组）或立即开始有限的抗逆转录病毒治疗直至1岁或2岁（早期抗逆转录病毒治疗组）。我们报告了接受延迟抗逆转录病毒治疗的婴儿与接受早期抗逆转录病毒治疗的婴儿的早期结局。在中位年龄为7.4周（四分位数范围，6.6至8.9）和CD 4百分比为35.2%（四分位数范围，29.1至41.2）时，125名婴儿被随机分配接受延迟治疗，252名婴儿被随机分配接受早期治疗。在中位随访40周后（四分位距，24 - 58），延迟治疗组中66%的婴儿开始抗逆转录病毒治疗。延迟治疗组有20名婴儿（16%）死亡，而早期治疗组有10名婴儿（4%）死亡（死亡风险比，0.24; 95%可信区间[CI]，0.11 ~ 0.51; P<0.001）。延迟治疗组中有32名婴儿（26%）与早期治疗组中有16名婴儿（6%），疾病进展到疾病控制和预防中心C期或严重B期（疾病进展的风险比，0.25; 95%CI，0.15 - 0.41; P<0.001）。在早期治疗组中，有4名婴儿因中性粒细胞减少症（3名）和贫血（1名）而被司他夫定替代齐多夫定;无药物永久停药。经过数据和安全监测委员会的审查，推迟治疗组进行了修改，该组中的婴儿都重新评估开始抗逆转录病毒治疗。早期艾滋病毒诊断和早期抗逆转录病毒治疗将早期婴儿死亡率降低76%，艾滋病毒进展降低75%。（ClinicalTrials.gov编号，NCT 00102960。）
In countries with a high seroprevalence of human immunodeficiency virus type 1 (HIV-1), HIV infection contributes significantly to infant mortality. We investigated antiretroviral-treatment strategies in the Children with HIV Early Antiretroviral Therapy (CHER) trial. HIV-infected infants 6 to 12 weeks of age with a CD4 lymphocyte percentage (the CD4 percentage) of 25% or more were randomly assigned to receive antiretroviral therapy (lopinavir–ritonavir, zidovudine, and lamivudine) when the CD4 percentage decreased to less than 20% (or 25% if the child was younger than 1 year) or clinical criteria were met (the deferred antiretroviral-therapy group) or to immediate initiation of limited antiretroviral therapy until 1 year of age or 2 years of age (the early antiretroviral-therapy groups). We report the early outcomes for infants who received deferred antiretroviral therapy as compared with early antiretroviral therapy. At a median age of 7.4 weeks (interquartile range, 6.6 to 8.9) and a CD4 percentage of 35.2% (interquartile range, 29.1 to 41.2), 125 infants were randomly assigned to receive deferred therapy, and 252 infants were randomly assigned to receive early therapy. After a median follow-up of 40 weeks (interquartile range, 24 to 58), antiretroviral therapy was initiated in 66% of infants in the deferred-therapy group. Twenty infants in the deferred-therapy group (16%) died versus 10 infants in the early-therapy groups (4%) (hazard ratio for death, 0.24; 95% confidence interval [CI], 0.11 to 0.51; P<0.001). In 32 infants in the deferred-therapy group (26%) versus 16 infants in the early-therapy groups (6%), disease progressed to Centers for Disease Control and Prevention stage C or severe stage B (hazard ratio for disease progression, 0.25; 95% CI, 0.15 to 0.41; P<0.001). Stavudine was substituted for zidovudine in four infants in the early-therapy groups because of neutropenia in three infants and anemia in one infant; no drugs were permanently discontinued. After a review by the data and safety monitoring board, the deferred-therapy group was modified, and infants in this group were all reassessed for initiation of antiretroviral therapy. Early HIV diagnosis and early antiretroviral therapy reduced early infant mortality by 76% and HIV progression by 75%. (ClinicalTrials.gov number, NCT00102960.)