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Hvidovre Hospital - en del af Københavns Universitetshospital
Udgivet

Contribution of Genetic Background and Data Collection on Adverse Events of Anti-human Immunodeficiency Virus (HIV) Drugs (D:A:D) Clinical Risk Score to Chronic Kidney Disease in Swiss HIV-infected Persons With Normal Baseline Estimated Glomerular Filtration Rate

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DOI

  • Léna G Dietrich
  • Catalina Barceló
  • Christian W Thorball
  • Lene Ryom
  • Felix Burkhalter
  • Barbara Hasse
  • Hansjakob Furrer
  • Maja Weisser
  • Ana Steffen
  • Enos Bernasconi
  • Matthias Cavassini
  • Sophie de Seigneux
  • Chantal Csajka
  • Jacques Fellay
  • Bruno Ledergerber
  • Philip E Tarr
Vis graf over relationer

Background. In human immunodeficiency virus (HIV), the relative contribution of genetic background, clinical risk factors, and antiretrovirals to chronic kidney disease (CKD) is unknown. Methods. We applied a case-control design and performed genome-wide genotyping in white Swiss HIV Cohort participants with normal baseline estimated glomerular filtration rate (eGFR >90 mL/minute/1.73 m 2). Univariable and multivariable CKD odds ratios (ORs) were calculated based on the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) score, which summarizes clinical CKD risk factors, and a polygenic risk score that summarizes genetic information from 86 613 single-nucleotide polymorphisms. Results. We included 743 cases with confirmed eGFR drop to <60 mL/minute/1.73 m 2 (n = 144) or ≥25% eGFR drop to <90 mL/ minute/1.73 m 2 (n = 599), and 322 controls (eGFR drop <15%). Polygenic risk score and D:A:D score contributed to CKD. In multivariable analysis, CKD ORs were 2.13 (95% confidence interval [CI], 1.55-2.97) in participants in the fourth (most unfavorable) vs first (most favorable) genetic score quartile; 1.94 (95% CI, 1.37-2.65) in the fourth vs first D:A:D score quartile; and 2.98 (95% CI, 2.02-4.66), 1.70 (95% CI, 1.29-2.29), and 1.83 (95% CI, 1.45-2.40), per 5 years of exposure to atazanavir/ritonavir, lopinavir/ritonavir, and tenofovir disoproxil fumarate, respectively. Participants in the first genetic score quartile had no increased CKD risk, even if they were in the fourth D:A:D score quartile. Conclusions. Genetic score increased CKD risk similar to clinical D:A:D score and potentially nephrotoxic antiretrovirals. Irrespective of D:A:D score, individuals with the most favorable genetic background may be protected against CKD.

OriginalsprogEngelsk
TidsskriftClinical infectious diseases : an official publication of the Infectious Diseases Society of America
Vol/bind70
Udgave nummer5
Sider (fra-til)890-897
Antal sider8
ISSN1058-4838
DOI
StatusUdgivet - 1 mar. 2020

Bibliografisk note

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

ID: 59944482