Publication
Rapid Progression of Kidney Dysfunction in Swiss People Living with HIV: Contribution of Polygenic Risk Score and D:A:D Clinical Risk Score
Journal Paper/Review - Nov 5, 2020
Dietrich Léna G, Tarr Philip E, Ledergerber Bruno, Fellay Jacques, Buvelot Hélène, Darling Kathrine E A, Bernasconi Enos, Schmid Patrick, Maja Weisser, Thurnheer Maria Christine, Hasse Barbara, Burkhalter Felix, Ryom Lene, Thorball Christian W, Swiss HIV Cohort Study
Units
PubMed
Doi
Citation
Type
Journal
Publication Date
Issn Electronic
Brief description/objective
BACKGROUND
In people with HIV (PWH), it is unknown whether genetic background associates with rapid progression of kidney dysfunction; i.e. eGFR decrease of >5mL/min/1.73m 2 per year for >3 consecutive years.
METHODS
We used time-to-event analyses to measure univariable and multivariable hazard ratios (HR) for rapid progression, based on the clinical D:A:D CKD risk score, antiretroviral exposures, and a polygenic risk score based on 14'769 genome-wide single nucleotide polymorphisms (SNPs) in white Swiss HIV Cohort Study participants.
RESULTS
We included 225 participants with rapid progression (median age 42 years, 76% male, median baseline eGFR 101 mL/min/1.73m 2) and 3378 rapid progression-free participants. In multivariable analysis, compared to participants with a low risk D:A:D CKD risk score, participants with medium and high risk had rapid progression-HR=1.30 (0.99-1.71) and 1.82 (1.28-2.60), respectively. Compared to the first (most favorable) polygenic risk score quartile, participants in the second, third and fourth (most unfavorable) quartiles had rapid progression-HR=1.39 (0.94-2.06), 1.52 (1.04-2.24) and 2.04 (1.41-2.94), respectively. Recent exposure to tenofovir disoproxil fumarate was associated with rapid progression (HR=1.36 [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.