IFNL3/4 polymorphisms are associated with AIDS-related Kaposi's sarcoma

Publication

IFNL3/4 polymorphisms are associated with AIDS-related Kaposi's sarcoma

Journal Paper/Review - Sep 17, 2018

Bibert Stéphanie, Bochud Pierre-Yves, Cavassini Matthias, Fellay Jacques, Osthoff Michael, Kaiser Laurent, Hoffmann Matthias, Günthard Huldrych F, Furrer Hansjakob, Bernasconi Enos, Tarr Philip E, Taffé Patrick, Wójtowicz Agnieszka, and the Swiss HIV Cohort Study

Citation

Bibert S, Bochud P, Cavassini M, Fellay J, Osthoff M, Kaiser L, Hoffmann M, Günthard H, Furrer H, Bernasconi E, Tarr P, Taffé P, Wójtowicz A, and the Swiss HIV Cohort Study. IFNL3/4 polymorphisms are associated with AIDS-related Kaposi's sarcoma. AIDS 2018

Type

Journal Paper/Review (English)

Journal

AIDS 2018

Publication Date

Sep 17, 2018

Issn Electronic

1473-5571

Brief description/objective

BACKGROUND
Kaposi's sarcoma (KS), the most common AIDS related cancer, represents a major public concern in resource-limited countries. Single nucleotide polymorphisms within the Interferon lambda 3/4 region (IFNL3/4) determine the expression, function of IFNL4, and influence the clinical course of an increasing number of viral infections.

OBJECTIVES
To analyze whether IFNL3/4 variants are associated with susceptibility to AIDS-related KS among men who have sex with men (MSM) enrolled in the Swiss HIV Cohort Study (SHCS).

METHODS
The risk of developing KS according to the carriage of IFNL3/4 SNPs rs8099917 and rs12980275 and their haplotypic combinations was assessed by using cumulative incidence curves and Cox regression models, accounting for relevant co-variables.

RESULTS
KS was diagnosed in 221 of 2558 MSM Caucasian SHCS participants. Both rs12980275 and rs8099917 were associated with an increased risk of KS (cumulative incidence 15% versus 10%, P = 0.01 and 16% versus 10%, P = 0.009 respectively). Diplotypes predicted to produce the active P70 form (cumulative incidence 16% versus 10%, P = 0.01) but not the less active S70 (cumulative incidence 11% versus 10%, P = 0.7) form of IFNL4 were associated with an increased risk of KS, compared to those predicted not to produce IFNL4.The associations remained significant in a multivariate Cox regression model after adjustment for age at infection, combination antiretroviral therapy, median CD4 T-cell count nadir and CD4 slopes (HR = 1.43, 95% confidence interval 1.06-1.93, P = 0.02 for IFLN P70 versus no IFNL4).

CONCLUSION
This study reports for the first time an association between IFNL3/4 polymorphisms and susceptibility to AIDS-related KS.