Rapid Progression of Kidney Dysfunction in People Living With HIV: Use of Polygenic and Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Risk Scores

Abstract Background In people with human immunodeficiency virus (PWH), it is unknown whether genetic background associates with rapid progression of kidney dysfunction (ie, estimated glomerular filtration rate [eGFR] decrease of >5mL/min/1.73m2 per year for ≥3 consecutive years). Methods We obtai...

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Bibliographic Details
Published in:The Journal of infectious diseases 2021-06, Vol.223 (12), p.2145-2153
Main Authors: Dietrich, Léna G, Thorball, Christian W, Ryom, Lene, Burkhalter, Felix, Hasse, Barbara, Thurnheer, Maria Christine, Weisser, Maja, Schmid, Patrick, Bernasconi, Enos, Darling, Kathrine E A, Buvelot, Hélène, Fellay, Jacques, Ledergerber, Bruno, Tarr, Philip E
Format: Article
Language:English
Subjects:
Anti-HIV Agents - adverse effects
Antiretroviral drugs
Cohort Studies
Data Collection
Disease Progression
Genomes
Glomerular Filtration Rate
Health risks
HIV
HIV Infections - complications
HIV Infections - drug therapy
Human immunodeficiency virus
Humans
Kidney - physiopathology
Kidney diseases
Kidney Diseases - complications
Polymorphism, Single Nucleotide
Risk Factors
Side effects
Single-nucleotide polymorphism
Switzerland
Tenofovir
Vitamin E
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Summary:Abstract Background In people with human immunodeficiency virus (PWH), it is unknown whether genetic background associates with rapid progression of kidney dysfunction (ie, estimated glomerular filtration rate [eGFR] decrease of >5mL/min/1.73m2 per year for ≥3 consecutive years). Methods We obtained univariable and multivariable hazard ratios (HR) for rapid progression, based on the clinical D:A:D chronic kidney disease (CKD) risk score, antiretroviral exposures, and a polygenic risk score based on 14 769 genome-wide single nucleotide polymorphisms in white Swiss HIV Cohort Study participants. Results We included 225 participants with rapid progression and 3378 rapid progression-free participants. In multivariable analysis, compared to participants with low D:A:D risk, participants with high risk had rapid progression (HR =  1.82 [95% CI, 1.28–2.60]). Compared to the first (favorable) polygenic risk score quartile, participants in the second, third, and fourth (unfavorable) quartiles had rapid progression (HR = 1.39 [95% CI, 0.94–2.06], 1.52 [95% CI, 1.04–2.24], and 2.04 [95% CI, 1.41–2.94], respectively). Recent exposure to tenofovir disoproxil fumarate was associated with rapid progression (HR = 1.36 [95% CI, 1.06–1.76]). Discussion An individual polygenic risk score is associated with rapid progression in Swiss PWH, when analyzed in the context of clinical and antiretroviral risk factors. We have previously associated genetic background with chronic kidney disease in people living with HIV (PWH). Here we show that an individual polygenic risk score is associated with rapid progression of kidney dysfunction in Swiss PWH.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/jiaa695