title: The IFNL3/4 ΔG variant increases susceptibility to cytomegalovirus retinitis among HIV-infected patients.
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.
  
  
  OBJECTIVE
  To analyze the association of newly identified IFNL3/4 variant rs368234815 with susceptibility to CMV-associated retinitis in a cohort of HIV-infected patients.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Bibert
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Wojtowicz
authors.forename: Patrick
authors.initials: P
authors.lastname: Taffé
authors.forename: Oriol
authors.initials: O
authors.lastname: Manuel
authors.forename: Enos
authors.initials: E
authors.lastname: Bernasconi
authors.forename: Hansjakob
authors.initials: H
authors.lastname: Furrer
authors.forename: Huldrych F
authors.initials: HF
authors.lastname: Günthard
authors.forename: Matthias
authors.initials: M
authors.lastname: Hoffmann
authors.forename: Laurent
authors.initials: L
authors.lastname: Kaiser
authors.forename: Michael
authors.initials: M
authors.lastname: Osthoff
authors.forename: Matthias
authors.initials: M
authors.lastname: Cavassini
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Bochud
mesh_terms: D000328:Adult; D017726:Cytomegalovirus Retinitis / Q000235:genetics* / Q000276:immunology*; D004198:Disease Susceptibility; D005260:Female; D056726:Genetic Association Studies; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013557:Switzerland; D000095022:Interferon Lambda
chemical_list: D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C579163:IFNL4 protein, human