抗反转录病毒治疗的 HIV 感染儿童的肝肾功能毒性及相关因素：一项前瞻性队列研究。

Hepatic and renal toxicity and associated factors among HIV-infected children on antiretroviral therapy: a prospective cohort study.

机构信息

Department of Pediatrics, College of Medicine and Health Sciences, Hawassa University, Hawassa, Ethiopia.

Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.

出版信息

HIV Med. 2019 Feb;20(2):147-156. doi: 10.1111/hiv.12693. Epub 2018 Nov 26.

DOI:10.1111/hiv.12693

PMID:30474906

Abstract

OBJECTIVES

The aim of the study was to investigate the prevalence of renal function and liver enzyme abnormalities among HIV-infected children, changes in prevalence with time on combination antiretroviral therapy (cART), and the factors associated with these abnormalities.

METHODS

A prospective cohort study was conducted among HIV-infected children < 18 years old (n = 705) who were on first-line cART. Liver enzymes, renal function, haematology, immunology and virological response were assessed at enrolment and followed bi-annually for 18 months. Liver fibrosis and cirrhosis were assessed using noninvasive markers including the aspartate aminotransferase (AST) to platelet ratio index (APRI) and fibrosis score (FIB-4).

RESULTS

The median age was 12 [interquartile range (IQR) 8-14] years; 53.3% of patients were male. At enrolment, the median cART duration was 3.3 (IQR 1.1-6.1) years; 177 (25.1%) and 83 (11.8%) patients had elevated AST and alanine aminotransferase (ALT), respectively. A tenth of the children had an APRI score > 0.5, suggesting liver fibrosis. Being on a zidovudine (ZDV)- or nevirapine (NVP)-based regimen and having a viral load > 1000 HIV-1 RNA copies/mL were significantly associated with elevated ALT. Twenty-four (3.4%) and 84 (12.1%) patients had elevated creatinine and blood urea nitrogen (BUN), respectively. As cART duration increased by 6 months, median BUN increased by 1.6 [95% confidence interval (CI) 0.4-2.7] mg/dL (P = 0.01); the glomerular filtration rate (GFR) decreased by 35.6 (95% CI 17.7-53.4) mL/min/1.73 m (P < 0.0001); and AST and ALT decreased by 1.4 (95% CI 0.4-2.5) IU/L (P = 0.01) and 1.4 (95% CI 0.2-2.6) IU/L (P = 0.01), respectively.

CONCLUSIONS

A high prevalence of liver enzyme and renal function abnormalities was observed at enrolment. Decreasing liver enzyme levels during follow-up are possibly reassuring, while the progressive reduction in GFR and the increase in BUN are worrisome and require further study.

摘要

目的

本研究旨在调查 HIV 感染儿童的肾功能和肝酶异常的流行情况，以及随着时间推移接受联合抗逆转录病毒治疗（cART）的变化情况，以及与这些异常相关的因素。

方法

对 705 名年龄<18 岁的接受一线 cART 的 HIV 感染儿童进行前瞻性队列研究。在入组时评估肝酶、肾功能、血液学、免疫学和病毒学反应，并在 18 个月内每 6 个月进行一次随访。使用非侵入性标志物，包括天门冬氨酸氨基转移酶（AST）与血小板比值指数（APRI）和纤维化评分（FIB-4）评估肝纤维化和肝硬化。

结果

中位年龄为 12 岁[四分位距（IQR）8-14 岁]；53.3%的患者为男性。入组时，cART 中位时间为 3.3 年（IQR 1.1-6.1 年）；177 名（25.1%）和 83 名（11.8%）患者的 AST 和丙氨酸氨基转移酶（ALT）升高。十分之一的儿童的 APRI 评分>0.5，提示存在肝纤维化。接受齐多夫定（ZDV）或奈韦拉平（NVP）为基础的方案和病毒载量>1000 HIV-1 RNA 拷贝/ml 与 ALT 升高显著相关。24 名（3.4%）和 84 名（12.1%）患者的血肌酐和血尿素氮（BUN）升高。随着 cART 时间延长 6 个月，中位 BUN 升高 1.6 [95%置信区间（CI）0.4-2.7]mg/dL（P=0.01）；肾小球滤过率（GFR）下降 35.6 [95%CI 17.7-53.4]mL/min/1.73 m（P<0.0001）；AST 和 ALT 分别下降 1.4 [95%CI 0.4-2.5]IU/L（P=0.01）和 1.4 [95%CI 0.2-2.6]IU/L（P=0.01）。