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Oxford University Press, Clinical Infectious Diseases, 2019

DOI: 10.1093/cid/ciz280

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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

This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

AbstractBackgroundIn human immunodeficiency virus (HIV), the relative contribution of genetic background, clinical risk factors, and antiretrovirals to chronic kidney disease (CKD) is unknown.MethodsWe 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 m2). 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.ResultsWe included 743 cases with confirmed eGFR drop to <60 mL/minute/1.73 m2 (n = 144) or ≥25% eGFR drop to <90 mL/minute/1.73 m2 (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.ConclusionsGenetic 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.