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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

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@article{5adf1809076d4586b694e9249b706888,
title = "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",
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.",
keywords = "antiretroviral therapy, clinical risk factors, genetics, HIV infection, rapid progression of kidney disease",
author = "Dietrich, {L{\'e}na G} and Thorball, {Christian W} and Lene Ryom and Felix Burkhalter and Barbara Hasse and Thurnheer, {Maria Christine} and Maja Weisser and Patrick Schmid and Enos Bernasconi and Darling, {Kathrine E A} and H{\'e}l{\`e}ne Buvelot and Jacques Fellay and Bruno Ledergerber and Tarr, {Philip E} and {Swiss HIV Cohort Study}",
note = "{\textcopyright} The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.",
year = "2021",
month = jun,
day = "15",
doi = "10.1093/infdis/jiaa695",
language = "English",
volume = "223",
pages = "2145--2153",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "University of Chicago Press",
number = "12",

}

RIS

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: journals.permissions@oup.com.

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

VL - 223

SP - 2145

EP - 2153

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 12

ER -

ID: 67940405