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

Publication

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

Journal Paper/Review - Aug 24, 2014

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

Citation

Bibert S, Bochud P, Cavassini M, Osthoff M, Kaiser L, Hoffmann M, Günthard H, Furrer H, Bernasconi E, Manuel O, Taffé P, Wójtowicz A. The IFNL3/4 ΔG variant increases susceptibility to cytomegalovirus retinitis among HIV-infected patients. AIDS 2014; 28:1885-9.

Type

Journal Paper/Review (English)

Journal

AIDS 2014; 28

Publication Date

Aug 24, 2014

Issn Electronic

1473-5571

Pages

1885-9

Brief description/objective

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.