Rapid progression of kidney dysfunction in Swiss people living with HIV: contribution of polygenic risk score and D:A:D clinical risk score

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