Chan Austin, Park Lawrence, Collins Lauren F, Cooper Curtis, Saag Michael, Dieterich Douglas, Sulkowski Mark, Naggie Susanna
Duke Clinical Research Institute, Durham, North Carolina.
Duke University School of Medicine, Durham, North Carolina.
Open Forum Infect Dis. 2019 Jan 24;6(1):ofy273. doi: 10.1093/ofid/ofy273. eCollection 2019 Jan.
Concomitant dosing of ledipasvir (LDV) and tenofovir disoproxil fumarate (TDF) results in an increased tenofovir (TFV) area under the curve (AUC). The aim of this study was to examine whether there was a correlation between the renal biomarkers retinol binding protein-4 (RBP-4) and β2 microglobulin (β2M) and tenofovir AUC.
The ION-4 trial enrolled HIV/hepatitis C virus-coinfected patients on nonpharmacologically boosted antiretroviral regimens with TDF-containing backbones. We assessed for a correlation between tenofovir AUC and urinary biomarkers and also for changes in serologic biomarkers with respect to clinically relevant changes in renal function (creatinine clearance decrease >25%, change in creatinine >0.2 mg/dL, change in proteinuria from negative/trace to ≥1+).
Three hundred thirty-five patients were enrolled in the ION-4 study; their demographic characteristics have been previously described. Both RBP-4 and β2M exhibited positive correlations with tenofovir AUC. Baseline and study levels of RBP-4 and β2M were higher for patients with increases in urine proteinuria and an absolute creatinine increase.
TFV exposure is associated with increased proximal tubule urine biomarkers in participants on ledipasvir/sofosbuvir and nonpharmacologically boosted TDF-based antiretroviral regimens. Baseline proximal tubule biomarkers may predict nephrotoxicity risk if events are prevalent. Further studies assessing the predictive role of these urine biomarkers may help guide medical decision-making and risk/benefit assessments in patients with risk factors for renal dysfunction.
雷迪帕韦（LDV）与替诺福韦酯富马酸盐（TDF）联合给药会导致替诺福韦（TFV）曲线下面积（AUC）增加。本研究的目的是检验肾生物标志物视黄醇结合蛋白-4（RBP-4）和β2微球蛋白（β2M）与替诺福韦AUC之间是否存在相关性。
ION-4试验纳入了接受含TDF主干的非药理学增强抗逆转录病毒方案治疗的HIV/丙型肝炎病毒合并感染患者。我们评估了替诺福韦AUC与尿液生物标志物之间的相关性，以及血清生物标志物相对于肾功能临床相关变化（肌酐清除率降低>25%、肌酐变化>0.2mg/dL、蛋白尿从阴性/微量变为≥1+）的变化。
ION-4研究共纳入335例患者；其人口统计学特征已在之前描述过。RBP-4和β2M均与替诺福韦AUC呈正相关。尿蛋白增加和肌酐绝对值增加的患者，其RBP-4和β2M的基线水平和研究水平更高。
在接受雷迪帕韦/索磷布韦和非药理学增强的基于TDF的抗逆转录病毒方案的参与者中，TFV暴露与近端肾小管尿液生物标志物增加有关。如果此类事件普遍存在，基线近端肾小管生物标志物可能预测肾毒性风险。进一步评估这些尿液生物标志物预测作用的研究可能有助于指导对有肾功能障碍风险因素患者的医疗决策和风险/获益评估。
