长期接受抗逆转录病毒治疗的 HIV 感染儿童的肝、肾、血液和炎症标志物。
Hepatic, Renal, Hematologic, and Inflammatory Markers in HIV-Infected Children on Long-term Suppressive Antiretroviral Therapy.
机构信息
Division of Pediatric Infectious Disease, Department of Pediatrics, University of Washington and Seattle Children's Research Institute.
Center for Biostatistics in AIDS Research, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
出版信息
J Pediatric Infect Dis Soc. 2017 Sep 1;6(3):e109-e115. doi: 10.1093/jpids/pix050.
BACKGROUND
Data on long-term toxicity of antiretroviral therapy (ART) in HIV-infected children are sparse. PENPACT-1 was an open-label trial in which HIV-infected children were assigned randomly to receive protease inhibitor (PI)- or nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based ART.
METHODS
We examined changes in clinical, immunologic, and inflammatory markers from baseline to year 4 in the subset of children in the PENPACT-1 study who experienced viral suppression between week 24 and year 4 of ART. Liver enzyme, creatinine, and cholesterol levels and hematologic parameters were assessed during the trial. Cystatin C, high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), d-dimer, and soluble CD14 (sCD14) were assayed from cryopreserved specimens.
RESULTS
Ninety-nine children (52 on PI-based and 47 on NNRTI-based ART) met inclusion criteria. The median age at initiation of ART was 6.5 years (interquartile range [IQR], 3.7-13.4 years), and 22% were aged <3 years at ART initiation; 56% of the PI-treated children received lopinavir/ritonavir, and 70% of NNRTI-treated children received efavirenz initially. We found no evidence of significant clinical toxicity in either group; growth, liver, kidney, and hematologic parameters either remained unchanged or improved between baseline and year 4. Total cholesterol levels increased modestly, but no difference between the groups was found. IL-6 and hs-CRP levels decreased more after 4 years in the NNRTI-based ART group. The median change in IL-6 level was -0.35 pg/ml in the PI-based ART group and -1.0 in the NNRTI-based ART group (P = .05), and the median change in hs-CRP level was 0.25 µg/ml in the PI-based ART group and -0.95 µg/ml in the NNRTI-based ART group (P = .005).
CONCLUSION
These results support the safety of prolonged ART use in HIV-infected children and suggest that suppressive NNRTI-based regimens can be associated with lower levels of systemic inflammation.
背景
关于抗逆转录病毒疗法（ART）在 HIV 感染儿童中的长期毒性的数据很少。PENPACT-1 是一项开放性试验，将 HIV 感染儿童随机分配接受蛋白酶抑制剂（PI）或非核苷类逆转录酶抑制剂（NNRTI）为基础的 ART。
方法
我们检查了 PENPACT-1 研究中那些在第 24 周至第 4 年期间实现病毒抑制的儿童亚组，从基线到第 4 年的临床、免疫和炎症标志物的变化。在试验期间评估了肝酶、肌酐和胆固醇水平以及血液学参数。从冷冻保存的标本中检测胱抑素 C、高敏 C 反应蛋白（hs-CRP）、白细胞介素 6（IL-6）、D-二聚体和可溶性 CD14（sCD14）。
结果
99 名儿童（52 名接受基于 PI 的治疗，47 名接受基于 NNRTI 的治疗）符合纳入标准。ART 开始时的中位年龄为 6.5 岁（四分位距 [IQR]，3.7-13.4 岁），22%的儿童在 ART 开始时年龄<3 岁；56%的 PI 治疗儿童接受洛匹那韦/利托那韦，70%的 NNRTI 治疗儿童最初接受依非韦伦。我们没有发现两组中存在显著临床毒性的证据；两组的生长、肝脏、肾脏和血液参数在基线和第 4 年均保持不变或改善。总胆固醇水平略有升高，但两组之间无差异。NNRTI 为基础的 ART 组的 IL-6 和 hs-CRP 水平在 4 年后下降更明显。PI 为基础的 ART 组的 IL-6 水平中位数变化为-0.35pg/ml，NNRTI 为基础的 ART 组为-1.0（P=0.05），PI 为基础的 ART 组 hs-CRP 水平中位数变化为 0.25µg/ml，NNRTI 为基础的 ART 组为-0.95µg/ml（P=0.005）。
结论
这些结果支持 HIV 感染儿童长期使用 ART 的安全性，并表明抑制性 NNRTI 为基础的方案可能与较低水平的全身炎症有关。
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