IFNL3/4 ΔG变异体增加了HIV感染患者患巨细胞病毒性视网膜炎的易感性。

The IFNL3/4 ΔG variant increases susceptibility to cytomegalovirus retinitis among HIV-infected patients.

作者信息

Bibert Stéphanie, Wojtowicz Agnieszka, Taffé Patrick, Manuel Oriol, Bernasconi Enos, Furrer Hansjakob, Günthard Huldrych F, Hoffmann Matthias, Kaiser Laurent, Osthoff Michael, Cavassini Matthias, Bochud Pierre-Yves

机构信息

aInfectious Diseases Service, Department of Medicine, University Hospital and University of Lausanne bInstitute for Social and Preventive Medicine, University (IUMSP), University Hospital of Lausanne, Lausanne cDivision of Infectious diseases, Regional hospital of Lugano, Lugano dDepartment of Infectious Diseases, Bern University Hospital and University of Bern, Bern eDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich fDivision of Infectious Diseases and Hospital Epidemiology, Department of Internal Medicine, Cantonal Hospital St Gallen, St Gallen gLaboratory of Virology, Division of Infectious Diseases and Division of Laboratory Medicine, University Hospital of Geneva and Medical School, University of Geneva, Geneva hDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland. *Matthias Cavassini and Pierre-Yves Bochud contributed equally to the manuscript †Members of the Swiss HIV Cohort Study group are listed in the acknowledgement section.

出版信息

AIDS. 2014 Aug 24;28(13):1885-9. doi: 10.1097/QAD.0000000000000379.

DOI:10.1097/QAD.0000000000000379

PMID:25259701

Abstract

BACKGROUND

Cytomegalovirus (CMV) retinitis is a major cause of visual impairment and blindness among patients with uncontrolled HIV infections. Whereas polymorphisms in interferon-lambda 3 (IFNL3, previously named IL28B) strongly influence the clinical course of hepatitis C, few studies examined the role of such polymorphisms in infections due to viruses other than hepatitis C virus.

OBJECTIVES

To analyze the association of newly identified IFNL3/4 variant rs368234815 with susceptibility to CMV-associated retinitis in a cohort of HIV-infected patients.

DESIGN AND METHODS

This retrospective longitudinal study included 4884 white patients from the Swiss HIV Cohort Study, among whom 1134 were at risk to develop CMV retinitis (CD4 nadir < 00 /μl and positive CMV serology). The association of CMV-associated retinitis with rs368234815 was assessed by cumulative incidence curves and multivariate Cox regression models, using the estimated date of HIV infection as a starting point, with censoring at death and/or lost follow-up.

RESULTS

A total of 40 individuals among 1134 patients at risk developed CMV retinitis. The minor allele of rs368234815 was associated with a higher risk of CMV retinitis (log-rank test P = 0.007, recessive mode of inheritance). The association was still significant in a multivariate Cox regression model (hazard ratio 2.31, 95% confidence interval 1.09-4.92, P = 0.03), after adjustment for CD4 nadir and slope, HAART and HIV-risk groups.

CONCLUSION

We reported for the first time an association between an IFNL3/4 polymorphism and susceptibility to AIDS-related CMV retinitis. IFNL3/4 may influence immunity against viruses other than HCV.

摘要

背景

巨细胞病毒（CMV）视网膜炎是未控制的HIV感染患者视力损害和失明的主要原因。虽然干扰素-λ3（IFNL3，以前称为IL28B）的多态性强烈影响丙型肝炎的临床病程，但很少有研究探讨此类多态性在丙型肝炎病毒以外的病毒感染中的作用。

目的

分析新发现的IFNL3/4变体rs368234815与HIV感染患者队列中CMV相关性视网膜炎易感性的关联。

设计与方法

这项回顾性纵向研究纳入了瑞士HIV队列研究中的4884名白人患者，其中1134人有发生CMV视网膜炎的风险（CD4最低点<200/μl且CMV血清学阳性）。以估计的HIV感染日期为起点，通过累积发病率曲线和多变量Cox回归模型评估CMV相关性视网膜炎与rs368234815的关联，并在死亡和/或失访时进行截尾。

结果

1134名有风险的患者中共有40人发生了CMV视网膜炎。rs368234815的次要等位基因与CMV视网膜炎的较高风险相关（对数秩检验P=0.007，隐性遗传模式）。在多变量Cox回归模型中，在调整了CD4最低点和斜率、高效抗逆转录病毒治疗（HAART）和HIV风险组后，该关联仍然显著（风险比2.31，95%置信区间1.09-4.92，P=0.03）。