Léna G Dietrich1,2, Christian W Thorball3,4, Lene Ryom5, Felix Burkhalter6, Barbara Hasse7, Maria Christine Thurnheer8, Maja Weisser9, Patrick Schmid10, Enos Bernasconi11, Kathrine E A Darling12, Hélène Buvelot13, Jacques Fellay3,4, Bruno Ledergerber7, Philip E Tarr1. 1. University Department of Medicine and Infectious Diseases Service, Kantonsspital Baselland, University of Basel, Bruderholz, Switzerland. 2. Department of Surgery and Traumatology, Gesundheitszentrum Fricktal, Rheinfelden, Switzerland. 3. Precision Medicine Unit, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland. 4. School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland. 5. Center of Excellence for Health, Immunity and Infections, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 6. University Department of Medicine and Nephrology Service, Kantonsspital Baselland, University of Basel, Bruderholz, Switzerland. 7. Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland. 8. Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland. 9. Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland. 10. Division of Infectious Diseases, Kantonsspital St Gallen, St Gallen, Switzerland. 11. Division of Infectious Diseases, Ospedale Regionale, Lugano, Switzerland. 12. Infectious Diseases Service, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland. 13. Division of Infectious Disease, Geneva University Hospital, Geneva, Switzerland.
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.
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.