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.
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 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.


RESULTS
We 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.


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.
['Dietrich|Léna G|LG|', 'Barceló|Catalina|C|', 'Thorball|Christian W|CW|', 'Ryom|Lene|L|', 'Burkhalter|Felix|F|', 'Hasse|Barbara|B|', 'Furrer|Hansjakob|H|', 'Weisser|Maja|M|', 'Steffen|Ana|A|', 'Bernasconi|Enos|E|', 'Cavassini|Matthias|M|', 'de Seigneux|Sophie|S|', 'Csajka|Chantal|C|', 'Fellay|Jacques|J|', 'Ledergerber|Bruno|B|', 'Tarr|Philip E|PE|']
D019380:Anti-HIV Agents D003625:Data Collection D000068617:Genetic Background D005919:Glomerular Filtration Rate D015658:HIV Infections D006801:Humans D004364:Pharmaceutical Preparations D051436:Renal Insufficiency, Chronic D012307:Risk Factors D013557:Switzerland
genetics chronic kidney disease clinical risk factors HIV infection antiretroviral therapy