1. No Association of IFNL4 Genotype With Opportunistic Infections and Cancers Among Men With Human Immunodeficiency Virus 1 Infection.
- Author
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Fang, Michelle Z, Jackson, Sarah S, Pfeiffer, Ruth M, Kim, Eun-Young, Chen, Sabrina, Hussain, Shehnaz K, Jacobson, Lisa P, Martinson, Jeremy, Prokunina-Olsson, Ludmila, Thio, Chloe L, Duggal, Priya, Wolinsky, Steven, and O'Brien, Thomas R
- Subjects
HIV infection complications ,OPPORTUNISTIC infections ,RESEARCH ,INTERLEUKINS ,CONFIDENCE intervals ,CYTOMEGALOVIRUS diseases ,SELF-evaluation ,SINGLE nucleotide polymorphisms ,HERPES simplex ,KAPOSI'S sarcoma ,INTERFERONS ,RISK assessment ,GENOTYPES ,DESCRIPTIVE statistics ,RESEARCH funding ,HIV ,LONGITUDINAL method ,PROPORTIONAL hazards models ,DISEASE risk factors ,DISEASE complications - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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