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在接受抗逆转录病毒治疗的HIV/丙型肝炎病毒合并感染患者中,HIV病毒学反弹而非病毒学波动可预测肝纤维化进展。

HIV virological rebounds but not blips predict liver fibrosis progression in antiretroviral-treated HIV/hepatitis C virus-coinfected patients.

作者信息

Cooper C, Rollet-Kurhajec K C, Young J, Vasquez C, Tyndall M, Gill J, Pick N, Walmsley S, Klein M B

机构信息

Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada; Canadian Institutes of Health Research Canadian HIV Trials Network, Vancouver, BC, Canada.

出版信息

HIV Med. 2015 Jan;16(1):24-31. doi: 10.1111/hiv.12168. Epub 2014 May 18.

Abstract

OBJECTIVES

Antiretroviral interruption is associated with liver fibrosis progression in HIV/hepatitis C virus (HCV) coinfection. It is not known what level of HIV viraemia affects fibrosis progression.

METHODS

We evaluated 288 HIV/HCV-coinfected cohort participants with undetectable HIV RNA (<50 HIV-1 RNA copies/mL) on two consecutive visits while on combination antiretroviral therapy (cART) without fibrosis [aspartate aminotransferase to platelet ratio index (APRI) <1.5], end-stage liver disease or HCV therapy. An HIV blip was defined as a viral load of ≥ 50 and <1000 copies/mL, preceded and followed by undetectable values. HIV rebound was defined as: (i) HIV RNA ≥ 50 copies/mL on two consecutive visits, or (ii) a single HIV RNA measurement ≥ 1000 copies/mL. Multivariate discrete-time proportional hazards models were used to assess the effect of different viraemia levels on liver fibrosis progression (APRI ≥ 1.5).

RESULTS

The mean age of the patients was 45 years, 74% were male, 81% reported a history of injecting drug use, 51% currently used alcohol and the median baseline CD4 count was 440 [interquartile range (IQR) 298, 609] cells/μL. Fifty-seven (20%) participants [12.4/100 person-years (PY); 95% confidence interval (CI) 9.2-15.7/100 PY] progressed to an APRI ≥ 1.5 over a mean 1.1 (IQR 0.6, 2.0) years of follow-up time at risk. Virological rebound [hazard ratio (HR) 2.3; 95% CI 1.1, 4.7] but not blips (HR 0.5; 95% CI 0.2, 1.1) predicted progression to APRI ≥ 1.5. Each additional 1 log10 copies/mL HIV RNA exposure (cumulative) was associated with a 20% increase in the risk of fibrosis progression (HR 1.2; 95% CI 1.0-1.3).

CONCLUSIONS

Liver fibrosis progression was associated with HIV rebound, but not blips, and with increasing cumulative exposure to HIV RNA, highlighting the importance of achieving and maintaining HIV suppression in the setting of HIV/HCV coinfection.

摘要

目的

在人类免疫缺陷病毒(HIV)/丙型肝炎病毒(HCV)合并感染中,抗逆转录病毒治疗中断与肝纤维化进展相关。目前尚不清楚何种水平的HIV病毒血症会影响纤维化进展。

方法

我们评估了288名HIV/HCV合并感染队列参与者,这些参与者在接受联合抗逆转录病毒治疗(cART)期间,连续两次就诊时HIV RNA检测不到(<50拷贝/mL),且无纤维化[天冬氨酸氨基转移酶与血小板比值指数(APRI)<1.5]、终末期肝病或HCV治疗史。HIV病毒波动定义为病毒载量≥50且<1000拷贝/mL,前后均为检测不到的值。HIV反弹定义为:(i)连续两次就诊时HIV RNA≥50拷贝/mL,或(ii)单次HIV RNA测量≥1000拷贝/mL。采用多变量离散时间比例风险模型评估不同病毒血症水平对肝纤维化进展(APRI≥1.5)的影响。

结果

患者的平均年龄为45岁,74%为男性,81%报告有注射吸毒史,51%目前饮酒,基线CD4计数中位数为440[四分位间距(IQR)298,609]个细胞/μL。在平均1.1(IQR 0.6,2.0)年的随访时间内,57名(20%)参与者[12.4/100人年(PY);95%置信区间(CI)9.2 - 15.7/100 PY]进展为APRI≥1.5。病毒学反弹[风险比(HR)2.3;95%CI 1.1,4.7]而非病毒波动(HR 0.5;95%CI 0.2,1.1)可预测进展为APRI≥1.5。每增加1 log10拷贝/mL的HIV RNA暴露(累积)与纤维化进展风险增加20%相关(HR 1.2;95%CI 1.0 - 1.3)。

结论

肝纤维化进展与HIV反弹相关,而非病毒波动,且与HIV RNA累积暴露增加相关,这突出了在HIV/HCV合并感染情况下实现并维持HIV抑制的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/50ef/4312483/c3d70d93993a/hiv0016-0024-f1.jpg

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