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

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/1.73m(2) 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.