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Prior exposure to thymidine analogues and didanosine is associated with long-lasting alterations in adipose tissue distribution and cardiovascular risk factors

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@article{05057c300aaf4f30a514069fdcf3f7be,
title = "Prior exposure to thymidine analogues and didanosine is associated with long-lasting alterations in adipose tissue distribution and cardiovascular risk factors",
abstract = "BACKGROUND: Thymidine analogues (TA) and didanosine (ddI) have been associated with redistribution of body fat from subcutaneous (SAT) to visceral (VAT) adipose tissue, which, in turn, is a risk factor for cardiovascular disease (CVD). We explored differences in adipose tissue distribution between people living with HIV (PLWH) with prior exposure to TA and/or ddI, without exposure, and uninfected controls and the association with CVD risk factors.METHODS: 761 PLWH from the COCOMO study and 2,283 age- and sex-matched uninfected controls from the CGPS study were included. PLWH were stratified according to prior exposure to TA and/or ddI. VAT and SAT were determined by abdominal CT-scan. Hypotheses were tested using regression analyses.RESULTS: Exposure to TA and/or ddI was associated with 21.6 cm larger VAT (13.8-29.3) compared to HIV infection without exposure. HIV-negative status was associated with similar VAT compared to HIV infection without exposure. Cumulative exposure to TA and/or ddI (3.7 cm per year [2.3-5.1]), but not time since discontinuation (-1.1 cm per year [-3.4-1.1]), was associated with VAT. Prior exposure to TA and/or ddI was associated with excess risk of hypertension (aOR 1.62 [1.13-2.31]), hypercholesterolemia (aOR 1.49 [1.06-2.11]), and low HDL (aOR 1.40 [0.99-1.99]).CONCLUSIONS: This study suggests a potentially irreversible and harmful association of TA and ddI with VAT accumulation, which appears be involved in the increased risk of hypertension, hypercholesterolemia, and low HDL found in PLWH with prior exposure to TA and/or ddI, even years after treatment discontinuation.",
keywords = "cardiovascular risk factors, didanosine, fat redistribution, thymidine analogs, visceral adipose tissue",
author = "Marco Gelpi and Shoaib Afzal and Andreas Fuchs and Jens Lundgren and Knudsen, {Andreas D} and Ninna Drivsholm and Amanda Mocroft and Anne-Mette Lebech and Birgitte Lindegaard and K{\"u}hl, {J{\o}rgen T} and Sigvardsen, {Per E} and Lars K{\o}ber and Nordestgaard, {B{\o}rge G} and Kofoed, {Klaus F} and Nielsen, {Susanne D}",
year = "2019",
month = "3",
day = "15",
doi = "10.1097/QAD.0000000000002119",
language = "English",
volume = "33",
pages = "675--683",
journal = "AIDS",
issn = "0269-9370",
publisher = "Lippincott Williams & Wilkins",
number = "4",

}

RIS

TY - JOUR

T1 - Prior exposure to thymidine analogues and didanosine is associated with long-lasting alterations in adipose tissue distribution and cardiovascular risk factors

AU - Gelpi, Marco

AU - Afzal, Shoaib

AU - Fuchs, Andreas

AU - Lundgren, Jens

AU - Knudsen, Andreas D

AU - Drivsholm, Ninna

AU - Mocroft, Amanda

AU - Lebech, Anne-Mette

AU - Lindegaard, Birgitte

AU - Kühl, Jørgen T

AU - Sigvardsen, Per E

AU - Køber, Lars

AU - Nordestgaard, Børge G

AU - Kofoed, Klaus F

AU - Nielsen, Susanne D

PY - 2019/3/15

Y1 - 2019/3/15

N2 - BACKGROUND: Thymidine analogues (TA) and didanosine (ddI) have been associated with redistribution of body fat from subcutaneous (SAT) to visceral (VAT) adipose tissue, which, in turn, is a risk factor for cardiovascular disease (CVD). We explored differences in adipose tissue distribution between people living with HIV (PLWH) with prior exposure to TA and/or ddI, without exposure, and uninfected controls and the association with CVD risk factors.METHODS: 761 PLWH from the COCOMO study and 2,283 age- and sex-matched uninfected controls from the CGPS study were included. PLWH were stratified according to prior exposure to TA and/or ddI. VAT and SAT were determined by abdominal CT-scan. Hypotheses were tested using regression analyses.RESULTS: Exposure to TA and/or ddI was associated with 21.6 cm larger VAT (13.8-29.3) compared to HIV infection without exposure. HIV-negative status was associated with similar VAT compared to HIV infection without exposure. Cumulative exposure to TA and/or ddI (3.7 cm per year [2.3-5.1]), but not time since discontinuation (-1.1 cm per year [-3.4-1.1]), was associated with VAT. Prior exposure to TA and/or ddI was associated with excess risk of hypertension (aOR 1.62 [1.13-2.31]), hypercholesterolemia (aOR 1.49 [1.06-2.11]), and low HDL (aOR 1.40 [0.99-1.99]).CONCLUSIONS: This study suggests a potentially irreversible and harmful association of TA and ddI with VAT accumulation, which appears be involved in the increased risk of hypertension, hypercholesterolemia, and low HDL found in PLWH with prior exposure to TA and/or ddI, even years after treatment discontinuation.

AB - BACKGROUND: Thymidine analogues (TA) and didanosine (ddI) have been associated with redistribution of body fat from subcutaneous (SAT) to visceral (VAT) adipose tissue, which, in turn, is a risk factor for cardiovascular disease (CVD). We explored differences in adipose tissue distribution between people living with HIV (PLWH) with prior exposure to TA and/or ddI, without exposure, and uninfected controls and the association with CVD risk factors.METHODS: 761 PLWH from the COCOMO study and 2,283 age- and sex-matched uninfected controls from the CGPS study were included. PLWH were stratified according to prior exposure to TA and/or ddI. VAT and SAT were determined by abdominal CT-scan. Hypotheses were tested using regression analyses.RESULTS: Exposure to TA and/or ddI was associated with 21.6 cm larger VAT (13.8-29.3) compared to HIV infection without exposure. HIV-negative status was associated with similar VAT compared to HIV infection without exposure. Cumulative exposure to TA and/or ddI (3.7 cm per year [2.3-5.1]), but not time since discontinuation (-1.1 cm per year [-3.4-1.1]), was associated with VAT. Prior exposure to TA and/or ddI was associated with excess risk of hypertension (aOR 1.62 [1.13-2.31]), hypercholesterolemia (aOR 1.49 [1.06-2.11]), and low HDL (aOR 1.40 [0.99-1.99]).CONCLUSIONS: This study suggests a potentially irreversible and harmful association of TA and ddI with VAT accumulation, which appears be involved in the increased risk of hypertension, hypercholesterolemia, and low HDL found in PLWH with prior exposure to TA and/or ddI, even years after treatment discontinuation.

KW - cardiovascular risk factors

KW - didanosine

KW - fat redistribution

KW - thymidine analogs

KW - visceral adipose tissue

U2 - 10.1097/QAD.0000000000002119

DO - 10.1097/QAD.0000000000002119

M3 - Journal article

VL - 33

SP - 675

EP - 683

JO - AIDS

JF - AIDS

SN - 0269-9370

IS - 4

ER -

ID: 58154540