Stéphanie Bibert1, Agnieszka Wojtowicz, Patrick Taffé, Oriol Manuel, Enos Bernasconi, Hansjakob Furrer, Huldrych F Günthard, Matthias Hoffmann, Laurent Kaiser, Michael Osthoff, Matthias Cavassini, Pierre-Yves Bochud. 1. 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.
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.
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-infectedpatients. 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.
Authors: Frank J Jenkins; Tsion Z Minas; Wei Tang; Tiffany H Dorsey; Stefan Ambs Journal: Prostate Cancer Prostatic Dis Date: 2022-04-25 Impact factor: 5.554
Authors: Eric G Meissner; Dongjun Chung; Betty Tsao; David W Haas; Netanya S Utay Journal: AIDS Res Hum Retroviruses Date: 2020-11-11 Impact factor: 1.723