Dirajlal-Fargo Sahera, Musiime Victor, Cook Adrian, Mirembe Grace, Kenny Julia, Jiang Ying, Debanne Sara, Klein Nigel, McComsey Grace A
From the *Case Western Reserve University, and†Rainbow Babies and Children's Hospital, Cleveland, Ohio; ‡Joint Clinical Research Centre, and §Makerere University College of Health Sciences, Kampala, Uganda; ¶MRC Clinical Trials Unit University College, and ‖Institute of Child Health University College, London, United Kingdom.
Pediatr Infect Dis J. 2017 Aug;36(8):761-767. doi: 10.1097/INF.0000000000001544.
Few studies have investigated metabolic complications in HIV-infected African children and their relation with inflammation.
We compared baseline and changes in insulin resistance [homeostatic model assessment of insulin resistance (HOMA-IR)] and in markers of inflammation over 48 weeks, in a subset of antiretroviral therapy (ART)-naive Ugandan children from the Children with HIV in Africa-Pharmacokinetics and Adherence/Acceptability of Simple Antiretroviral Regimens trial randomized to zidovudine-, stavudine- or abacavir (ABC)-based regimen. Nonparametric methods were used to explore between-group and within-group differences, and multivariable analysis to assess associations of HOMA-IR.
One-hundred eighteen children were enrolled, and median age (interquartile range) was 2.8 years (1.7-4.3). Baseline median HOMA-IR (interquartile range) was 0.49 (0.38-1.07) and similar between the arms. At week 48, median relative changes in HOMA-IR were 14% (-29% to 97%) in the zidovudine arm, -1% (-30% to 69%) in the stavudine arm and 6% (-34% to 124%) in the ABC arm (P ≤ 0.03 for all the arms compared with baseline, but P = 0.90 for between-group differences). Several inflammation markers significantly decreased in all study arms; soluble CD14 increased on ABC and did not change in the other 2 arms. In multivariate analysis, only changes in soluble CD163 were positively associated with HOMA-IR changes.
In ART-naive Ugandan children, HOMA-IR changed significantly after 48 weeks of ART and correlated with monocyte activation.
很少有研究调查感染艾滋病毒的非洲儿童的代谢并发症及其与炎症的关系。
在非洲艾滋病毒儿童-简单抗逆转录病毒治疗方案的药代动力学和依从性/可接受性试验中,我们比较了一组未接受过抗逆转录病毒治疗(ART)的乌干达儿童在48周内胰岛素抵抗[胰岛素抵抗稳态模型评估(HOMA-IR)]的基线水平和变化以及炎症标志物的变化,这些儿童被随机分配到基于齐多夫定、司他夫定或阿巴卡韦(ABC)的治疗方案组。采用非参数方法探讨组间和组内差异,并进行多变量分析以评估HOMA-IR的相关性。
共招募了118名儿童,中位年龄(四分位间距)为2.8岁(1.7 - 4.3岁)。基线时HOMA-IR的中位值(四分位间距)为0.49(0.38 - 1.07),各治疗组之间相似。在第48周时,齐多夫定组HOMA-IR的中位相对变化为14%(-29%至97%),司他夫定组为-1%(-30%至69%),ABC组为6%(-34%至124%)(与基线相比,所有治疗组P≤0.03,但组间差异P = 0.90)。所有研究组的几种炎症标志物均显著下降;ABC组可溶性CD14升高,其他两组未变化。在多变量分析中,只有可溶性CD163的变化与HOMA-IR的变化呈正相关。
在未接受过ART治疗的乌干达儿童中,ART治疗48周后HOMA-IR发生显著变化,并与单核细胞活化相关。