Palumbo P E, Raskino C, Fiscus S, Pahwa S, Fowler M G, Spector S A, Englund J A, Baker C J
Department of Pediatrics, University of Medicine and Dentistry of New Jersey, Newark 07103, USA.
JAMA. 1998 Mar 11;279(10):756-61. doi: 10.1001/jama.279.10.756.
Pediatric human immunodeficiency virus (HIV) infection has unique viral pathogenetic features that preclude routine extrapolation from adult studies and require specific analysis.
To evaluate the prognostic value of 2 key laboratory markers-plasma RNA and CD4+ lymphocyte count-for HIV disease progression in infants and children and to establish targeted values for optimal outcome.
Data from a cohort of 566 infants and children who participated in a randomized, placebo-controlled trial of nucleoside reverse transcriptase inhibitors (ACTG 152) were analyzed. The trial was conducted between 1991 and 1995 and enrolled a heterogeneous cohort of antiretroviral therapy-naive children (age, 3 months to 18 years); patients had a median follow-up of 32 months.
The trial clinical end points consisted of time to first HIV disease progression (growth failure, decline in neurologic or neurodevelopmental function, opportunistic infections) or death.
Baseline plasma RNA levels were high (age group medians, 5 x 10(4) to >10(6) copies/mL), and both baseline RNA and CD4+ lymphocyte count were independently predictive of subsequent clinical course. Risk reduction for disease progression between 49% and 64% was observed for each log10 reduction in baseline RNA and was linear without suggestion of a threshold or age effect. Disease progression predictive power was enhanced by the combined use of plasma RNA and CD4+ cell count. Marker values of less than 10000 copies/mL for plasma RNA and greater than 500 x 10(6)/L (<6.5 years of age) or greater than 200 x 10(6)/L (>6.5 years) for CD4+ cell count were associated with a 2-year disease progression rate of less than 5%.
Two key laboratory markers--plasma RNA and CD4+ lymphocyte count-are independent predictors of clinical course among HIV-infected infants and children. The linear, age-independent relationship between log10 plasma RNA and relative risk of disease progression strongly supports therapeutic efforts to achieve plasma virus levels as low as possible.
儿童人类免疫缺陷病毒（HIV）感染具有独特的病毒致病特征，这使得无法从成人研究中进行常规推断，需要进行具体分析。
评估两个关键实验室指标——血浆RNA和CD4+淋巴细胞计数——对婴幼儿和儿童HIV疾病进展的预后价值，并确定实现最佳结果的目标值。
分析了566名婴幼儿和儿童的数据，这些儿童参与了一项核苷类逆转录酶抑制剂的随机、安慰剂对照试验（ACTG 152）。该试验于1991年至1995年进行，纳入了一组未经抗逆转录病毒治疗的异质性儿童队列（年龄3个月至18岁）；患者的中位随访时间为32个月。
试验临床终点包括首次出现HIV疾病进展（生长发育迟缓、神经或神经发育功能下降、机会性感染）或死亡的时间。
基线血浆RNA水平较高（年龄组中位数为5×10⁴至>10⁶拷贝/mL），基线RNA和CD4+淋巴细胞计数均独立预测后续临床病程。基线RNA每降低1个对数10，疾病进展风险降低49%至64%，呈线性关系，无阈值或年龄效应的迹象。血浆RNA和CD4+细胞计数联合使用可增强疾病进展预测能力。血浆RNA小于10000拷贝/mL，CD4+细胞计数在6.5岁以下大于500×10⁶/L或6.5岁以上大于200×10⁶/L，与2年疾病进展率低于5%相关。
两个关键实验室指标——血浆RNA和CD4+淋巴细胞计数——是HIV感染婴幼儿和儿童临床病程的独立预测指标。血浆RNA对数10与疾病进展相对风险之间的线性、与年龄无关的关系有力地支持了尽可能降低血浆病毒水平的治疗努力。
