简短报告：在接受二线抗逆转录病毒治疗的亚洲HIV感染儿童和青少年中，洛匹那韦头发浓度是病毒血症的最强预测指标。
Brief Report: Lopinavir Hair Concentrations Are the Strongest Predictor of Viremia in HIV-Infected Asian Children and Adolescents on Second-Line Antiretroviral Therapy.
作者信息
Pintye Jillian, Bacchetti Peter, Teeraananchai Sirinya, Kerr Stephen, Prasitsuebsai Wasana, Singtoroj Thida, Kuncze Karen, Louie Alexander, Koss Catherine A, Jin Chengshi, Phung Nhi, Horng Howard, Sohn Annette H, Gandhi Monica
机构信息
*Department of Global Health, University of Washington, Seattle, WA; †Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA; ‡HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand; §The Kirby Institute, University of New South Wales, Sydney, Australia; ‖GlaxoSmithKline (Thailand) Ltd., Bangkok, Thailand; ¶TREAT Asia/amfAR-The Foundation for AIDS Research, Bangkok, Thailand; and #Department of Medicine, University of California, San Francisco, San Francisco, CA.
出版信息
J Acquir Immune Defic Syndr. 2017 Dec 1;76(4):367-371. doi: 10.1097/QAI.0000000000001527.
BACKGROUND
Children/adolescents display suboptimal antiretroviral therapy (ART) adherence and outcomes versus adults. Hair ART concentrations are objective adherence measures that predict viremia in adults but longitudinal data on hair levels in pediatric populations is limited. We assessed the predictive utility of hair lopinavir (LPV) levels on viremia among youth on second-line ART.
METHODS
We examined predictors of viremia (HIV-1 RNA >400 and >1000 copies/mL) at least 24 weeks after switch to LPV-based second-line ART in a cohort of HIV-infected Asian children followed between 2011 and 2014. Small hair samples, HIV-1 RNA, and self-reported adherence were collected biannually. Hair concentrations of LPV were measured through liquid chromatography/tandem mass spectrometry using validated methods. Time-to-first viremia was examined using discrete-time Cox models.
RESULTS
Overall, 244 children met the inclusion criteria for the present analysis. Approximately half (55%) were boys and the median age 10 years [interquartile range (IQR) 7-13]; 40% were older than 11 years. At switch to second-line ART, median CD4 count was 300 (IQR 146-547) cells/mm and median HIV-RNA level was 5.0 (IQR 4.3-5.6) log10/mL. Median time of study follow-up was 48 weeks and a median of 3 (range 1-5) hair samples were collected from each participant. Adjusting for age, sex, country, self-reported adherence, CD4, and HIV-RNA, higher LPV hair concentrations were the strongest predictor of lower odds of viremia (HIV-RNA >400 copies/mL adjusted odds ratio = 0.41 per doubling in hair concentration, 95% confidence interval: 0.29 to 0.58, P < 0.001; HIV-RNA >1000 copies/mL, adjusted odds ratio = 0.54, 95% confidence interval: 0.45 to 0.65, P < 0.001).
CONCLUSIONS
Hair concentrations predict viremia among children with HIV on second-line ART and could guide clinical decisions for this population.
背景
与成人相比，儿童/青少年的抗逆转录病毒疗法（ART）依从性和治疗效果欠佳。头发中的ART浓度是客观的依从性指标，可预测成人的病毒血症，但关于儿科人群头发中药物浓度的纵向数据有限。我们评估了二线ART治疗的青少年中，头发中洛匹那韦（LPV）水平对病毒血症的预测效用。
方法
在2011年至2014年随访的一组感染HIV的亚洲儿童队列中，我们检查了转换至基于LPV的二线ART至少24周后病毒血症（HIV-1 RNA>400和>1000拷贝/mL）的预测因素。每半年收集一次少量头发样本、HIV-1 RNA和自我报告的依从性数据。使用经过验证的方法通过液相色谱/串联质谱法测量头发中LPV的浓度。使用离散时间Cox模型检查首次出现病毒血症的时间。
结果
总体而言，244名儿童符合本分析的纳入标准。大约一半（55%）为男孩，中位年龄10岁[四分位间距（IQR）7-13岁]；40%的儿童年龄超过11岁。转换至二线ART时，CD4细胞计数中位数为300（IQR 146-547）个/mm，HIV-RNA水平中位数为5.0（IQR 4.3-5.6）log10/mL。研究随访的中位时间为48周，每位参与者收集的头发样本中位数为3份（范围1-5份）。调整年龄、性别、国家、自我报告的依从性、CD4和HIV-RNA后，较高的LPV头发浓度是病毒血症几率降低的最强预测因素（HIV-RNA>400拷贝/mL，头发浓度每增加一倍，调整后的优势比=0.41，95%置信区间：0.29至0.58，P<0.001；HIV-RNA>1000拷贝/mL，调整后的优势比=0.54，95%置信区间：0.45至0.65，P<0.001）。
结论
头发中的药物浓度可预测接受二线ART治疗的HIV感染儿童的病毒血症，并可为该人群的临床决策提供指导。
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