TY - JOUR
T1 - Rapid Progression of Kidney Dysfunction in People Living With HIV
T2 - Use of Polygenic and Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Risk Scores
AU - Dietrich, Léna G
AU - Thorball, Christian W
AU - Ryom, Lene
AU - Burkhalter, Felix
AU - Hasse, Barbara
AU - Thurnheer, Maria Christine
AU - Weisser, Maja
AU - Schmid, Patrick
AU - Bernasconi, Enos
AU - Darling, Kathrine E A
AU - Buvelot, Hélène
AU - Fellay, Jacques
AU - Ledergerber, Bruno
AU - Tarr, Philip E
AU - Swiss HIV Cohort Study
N1 - © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected].
PY - 2021/6/15
Y1 - 2021/6/15
N2 - 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.
AB - 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.
KW - antiretroviral therapy
KW - clinical risk factors
KW - genetics
KW - HIV infection
KW - rapid progression of kidney disease
UR - http://www.scopus.com/inward/record.url?scp=85108386785&partnerID=8YFLogxK
U2 - 10.1093/infdis/jiaa695
DO - 10.1093/infdis/jiaa695
M3 - Journal article
C2 - 33151293
SN - 0022-1899
VL - 223
SP - 2145
EP - 2153
JO - The Journal of infectious diseases
JF - The Journal of infectious diseases
IS - 12
M1 - jiaa695
ER -