No Association of IFNL4 Genotype with Opportunistic Infections and Cancers among Men with Human Immunodeficiency Virus 1 Infection

Michelle Z. Fang, Sarah S. Jackson, Ruth M. Pfeiffer, Eun-Young Kim, Sabrina Chen, Shehnaz K. Hussain, Lisa P. Jacobson, Jeremy Martinson, Ludmila Prokunina-Olsson, Chloe L. Thio, Priya Duggal, Steven Wolinsky, Thomas R. O'Brien

Research output: Contribution to journalArticlepeer-review


Background: IFNL4 genetic variants that are strongly associated with clearance of hepatitis C virus have been linked to risk of certain opportunistic infections (OIs) and cancers, including Kaposi sarcoma, cytomegalovirus infection, and herpes simplex virus infection. As the interferon (IFN) λ family plays a role in response to viral, bacterial, and fungal infections, IFNL4 genotype might affect risk for a wide range of OIs/cancers. Methods: We examined associations between genotype for the functional IFNL4 rs368234815 polymorphism and incidence of 16 OIs/cancers among 2310 men with human immunodeficiency virus (2038 white; 272 black) enrolled in the Multicenter AIDS Cohort Study during 1984-1990. Our primary analyses used Cox proportional hazards models adjusted for self-reported racial ancestry to estimate hazard ratios with 95% confidence intervals, comparing participants with the genotypes that generate IFN-λ4 and those with the genotype that abrogates IFN-λ4. We censored follow-up at the introduction of highly effective antiretroviral therapies. Results: We found no statistically significant association between IFNL4 genotype and the incidence of Kaposi sarcoma (hazard ratio, 0.92 [95% confidence interval,. 76-1.11]), cytomegalovirus infection (0.94 [.71-1.24]), herpes simplex virus infection (1.37 [.68-2.93]), or any other OI/cancer. We observed consistent results using additive genetic models and after controlling for CD4 cell count through time-dependent adjustment or restriction to participants with a low CD4 cell count. Conclusions: The absence of associations between IFNL4 genotype and these OIs/cancers provides evidence that this gene does not affect the risk of disease from opportunistic pathogens.

Original languageEnglish (US)
Pages (from-to)521-527
Number of pages7
JournalClinical Infectious Diseases
Issue number3
StatePublished - Feb 1 2023


  • cytomegalovirus
  • genetics
  • herpes simplex virus
  • interferon λ
  • Kaposi sarcoma

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases


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