Neukam Karin, Mira José A, Collado Antonio, Rivero-Juárez Antonio, Monje-Agudo Patricia, Ruiz-Morales Josefa, Ríos María José, Merino Dolores, Téllez Francisco, Pérez-Camacho Inés, Gálvez-Contreras María Carmen, Rivero Antonio, Pineda Juan A
Unit of Infectious Diseases and Microbiology, Hospital Universitario de Valme, Seville, Spain.
Instituto de Biomedicina de Sevilla (IBiS), Seville, Spain.
PLoS One. 2016 Feb 5;11(2):e0148104. doi: 10.1371/journal.pone.0148104. eCollection 2016.
To assess the current frequency of ART-associated grade 3-4 transaminase elevations (TE) and grade 4 total bilirubin elevations (TBE) in HIV-infected patients with chronic hepatitis B and/or C, who start a new regimen of ART.
A total of 192 pre-treated or treatment-naive HIV infected patients with HBV and/or HCV-coinfection who started ART in eight Southern Spanish centers from July/2011-December/2013, were followed for 12 months in this prospective study.
Forty-one (21.4%) subjects had been naïve to ART, median (IQR) follow-up was 11.6 (5.6-12.9) months. The most frequently initiated NRTI were tenofovir/emtricitabine [49 patients (25.5%)]. Eighty-nine (46.4%) patients started a ritonavir-boosted protease inhibitor and 77 (40.1%) individuals a NNRTI. Raltegravir and maraviroc were initiated in 24 (12.5%) and 9 (4.7%) individuals. Ten [5.21%; 95% confidence interval (CI): 2.53%-9.37%] patients presented grade 3 TE, while 8 (4.17%; 95%CI: 1.82%-8.04%) subjects showed grade 4 TBE. No episodes of grade 4 TE or ART discontinuation due to hepatotoxic events were observed. The use of ritonavir-boosted atazanavir was the only independent predictor for grade 4 TBE [adjusted odds ratio: 7.327 (95%CI: 1.417-37.89); p = 0.018] in an analysis adjusted for age, sex and baseline HIV-RNA levels, while no factor could be independently associated with grade 3-4 TE.
Currently, the frequency of severe ART-associated TE and TBE under real-life conditions in patients with chronic viral hepatitis is similar to what has been reported previously. However, episodes of grade 4 TE are less frequent and severe TE appears to be of lesser concern.
评估开始新抗逆转录病毒治疗（ART）方案的慢性乙型和/或丙型肝炎合并感染的HIV感染者中，ART相关3 - 4级转氨酶升高（TE）和4级总胆红素升高（TBE）的当前发生率。
本前瞻性研究对2011年7月至2013年12月期间在西班牙南部八个中心开始接受ART治疗的192例经治或初治的HBV和/或HCV合并感染的HIV感染者进行了为期12个月的随访。
41例（21.4%）受试者为ART初治患者，中位（四分位间距）随访时间为11.6（5.6 - 12.9）个月。最常起始的核苷类逆转录酶抑制剂（NRTI）是替诺福韦/恩曲他滨[49例患者（25.5%）]。89例（46.4%）患者开始使用利托那韦增强的蛋白酶抑制剂，77例（40.1%）患者开始使用非核苷类逆转录酶抑制剂（NNRTI）。24例（12.5%）患者起始了拉替拉韦，9例（4.7%）患者起始了马拉维罗。10例[5.21%；95%置信区间（CI）：2.53% - 9.37%]患者出现3级TE，而8例（4.17%；95%CI：1.82% - 8.04%）受试者出现4级TBE。未观察到4级TE发作或因肝毒性事件导致ART停药的情况。在对年龄、性别和基线HIV - RNA水平进行校正的分析中，使用利托那韦增强的阿扎那韦是4级TBE的唯一独立预测因素[校正比值比：7.327（95%CI：1.417 - 37.89）；p = 0.018]，而没有因素能与3 - 4级TE独立相关。
目前，在慢性病毒性肝炎患者的实际生活条件下，严重的ART相关TE和TBE的发生率与先前报道相似。然而，4级TE发作较少，严重TE似乎不太令人担忧。
