Dietrich, Lena G.Barcelo, CatalinaThorball, Christian W.Ryom, LeneBurkhalter, FelixHasse, BarbaraFurrer, HansjakobWeisser, MajaSteffen, AnaBernasconi, EnosCavassini, Matthiasde Seigneux, SophieCsajka, ChantalFellay, JacquesLedergerber, BrunoTarr, Philip E.2020-04-032020-04-032020-04-032020-03-0110.1093/cid/ciz280https://infoscience.epfl.ch/handle/20.500.14299/167929WOS:000520551800027Background. 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.ImmunologyInfectious DiseasesMicrobiologyhiv infectionchronic kidney diseasegeneticsclinical risk factorsantiretroviral therapysingle-nucleotide polymorphismscoronary-artery-diseaseassociationadultspredictionvariantstext::journal::journal article::research article