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  4. 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
 
research article

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

Dietrich, Lena G.
•
Barcelo, Catalina
•
Thorball, Christian W.
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March 1, 2020
Clinical Infectious Diseases

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.

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Type
research article
DOI
10.1093/cid/ciz280
Web of Science ID

WOS:000520551800027

Author(s)
Dietrich, Lena G.
•
Barcelo, Catalina
•
Thorball, Christian W.
•
Ryom, Lene
•
Burkhalter, Felix
•
Hasse, Barbara
•
Furrer, Hansjakob
•
Weisser, Maja
•
Steffen, Ana
•
Bernasconi, Enos
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Date Issued

2020-03-01

Publisher

OXFORD UNIV PRESS INC

Published in
Clinical Infectious Diseases
Volume

70

Issue

5

Start page

890

End page

897

Subjects

Immunology

•

Infectious Diseases

•

Microbiology

•

hiv infection

•

chronic kidney disease

•

genetics

•

clinical risk factors

•

antiretroviral therapy

•

single-nucleotide polymorphisms

•

coronary-artery-disease

•

association

•

adults

•

prediction

•

variants

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
UPFELLAY  
Available on Infoscience
April 3, 2020
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/167929
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