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

Marco Gelpi; Shoaib Afzal; Andreas Fuchs; Jens Lundgren; Andreas D Knudsen; Ninna Drivsholm; Amanda Mocroft; Anne-Mette Lebech; Birgitte Lindegaard; Jørgen T. Kühl; Per E. Sigvardsen; Lars Køber; Børge G. Nordestgaard; Klaus F. Kofoed; Susanne D. Nielsen

doi:10.1097/QAD.0000000000002119

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

Marco Gelpi, Shoaib Afzal, Andreas Fuchs, Jens Lundgren, Andreas D Knudsen, Ninna Drivsholm, Amanda Mocroft, Anne-Mette Lebech, Birgitte Lindegaard, Jørgen T. Kühl, Per E. Sigvardsen, Lars Køber, Børge G. Nordestgaard, Klaus F. Kofoed, Susanne D. Nielsen

Department of Clinical Medicine

14 Citations (Scopus)

Abstract

Background:Thymidine analogs and didanosine (ddI) have been associated with redistribution of body fat from subcutaneous adipose tissue (SAT) to visceral adipose tissue (VAT), which, in turn, is a risk factor for cardiovascular disease. We explored differences in adipose tissue distribution between people living with HIV (PLWH) with prior exposure to thymidine analogs and/or ddI, without exposure, and uninfected controls and the association with cardiovascular disease risk factors.Methods:In all, 761 PLWH from the Copenhagen Comorbidity in HIV Infection study, and 2283 age and sex-matched uninfected controls from the Copenhagen General Population Study were included. PLWH were stratified according to prior exposure to thymidine analogs and/or ddI. VAT and SAT were determined by abdominal computed tomography scan. Hypotheses were tested using regression analyses.Results:Exposure to thymidine analogs and/or ddI was associated with 21.6cm² 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 thymidine analogs and/or ddI [3.7cm² per year (2.3-5.1)], but not time since discontinuation [-1.1cm² per year (-3.4 to 1.1)], was associated with VAT. Prior exposure to thymidine analogs and/or ddI was associated with excess risk of hypertension [adjusted odds ratio (aOR) 1.62 (1.13-2.31)], hypercholesterolemia [aOR 1.49 (1.06-2.11)], and low high-density lipoprotein [aOR 1.40 (0.99-1.99)].Conclusions:This study suggests a potentially irreversible and harmful association of thymidine analogs and ddI with VAT accumulation, which appears be involved in the increased risk of hypertension, hypercholesterolemia, and low high-density lipoprotein found in PLWH with prior exposure to thymidine analogs and/or ddI, even years after treatment discontinuation.

Original language	English
Journal	AIDS
Volume	33
Issue number	4
Pages (from-to)	675-683
Number of pages	9
ISSN	0269-9370
DOIs	https://doi.org/10.1097/QAD.0000000000002119
Publication status	Published - 15 Mar 2019

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Gelpi, M., Afzal, S., Fuchs, A., Lundgren, J., Knudsen, A. D., Drivsholm, N., Mocroft, A., Lebech, A.-M., Lindegaard, B., Kühl, J. T., Sigvardsen, P. E., Køber, L., Nordestgaard, B. G., Kofoed, K. F., & Nielsen, S. D. (2019). Prior exposure to thymidine analogs and didanosine is associated with long-lasting alterations in adipose tissue distribution and cardiovascular risk factors. AIDS, 33(4), 675-683. https://doi.org/10.1097/QAD.0000000000002119

Gelpi, M, Afzal, S, Fuchs, A, Lundgren, J, Knudsen, AD, Drivsholm, N, Mocroft, A, Lebech, A-M , Lindegaard, B, Kühl, JT, Sigvardsen, PE, Køber, L , Nordestgaard, BG , Kofoed, KF & Nielsen, SD 2019, 'Prior exposure to thymidine analogs and didanosine is associated with long-lasting alterations in adipose tissue distribution and cardiovascular risk factors', AIDS, vol. 33, no. 4, pp. 675-683. https://doi.org/10.1097/QAD.0000000000002119

@article{eb12821c88f94c2e9d1516113b52071d,

title = "Prior exposure to thymidine analogs and didanosine is associated with long-lasting alterations in adipose tissue distribution and cardiovascular risk factors",

abstract = "Background:Thymidine analogs and didanosine (ddI) have been associated with redistribution of body fat from subcutaneous adipose tissue (SAT) to visceral adipose tissue (VAT), which, in turn, is a risk factor for cardiovascular disease. We explored differences in adipose tissue distribution between people living with HIV (PLWH) with prior exposure to thymidine analogs and/or ddI, without exposure, and uninfected controls and the association with cardiovascular disease risk factors.Methods:In all, 761 PLWH from the Copenhagen Comorbidity in HIV Infection study, and 2283 age and sex-matched uninfected controls from the Copenhagen General Population Study were included. PLWH were stratified according to prior exposure to thymidine analogs and/or ddI. VAT and SAT were determined by abdominal computed tomography scan. Hypotheses were tested using regression analyses.Results:Exposure to thymidine analogs and/or ddI was associated with 21.6cm2 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 thymidine analogs and/or ddI [3.7cm2 per year (2.3-5.1)], but not time since discontinuation [-1.1cm2 per year (-3.4 to 1.1)], was associated with VAT. Prior exposure to thymidine analogs and/or ddI was associated with excess risk of hypertension [adjusted odds ratio (aOR) 1.62 (1.13-2.31)], hypercholesterolemia [aOR 1.49 (1.06-2.11)], and low high-density lipoprotein [aOR 1.40 (0.99-1.99)].Conclusions:This study suggests a potentially irreversible and harmful association of thymidine analogs and ddI with VAT accumulation, which appears be involved in the increased risk of hypertension, hypercholesterolemia, and low high-density lipoprotein found in PLWH with prior exposure to thymidine analogs and/or ddI, even years after treatment discontinuation.",

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 = mar,

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",

}

TY - JOUR

T1 - Prior exposure to thymidine analogs 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 analogs and didanosine (ddI) have been associated with redistribution of body fat from subcutaneous adipose tissue (SAT) to visceral adipose tissue (VAT), which, in turn, is a risk factor for cardiovascular disease. We explored differences in adipose tissue distribution between people living with HIV (PLWH) with prior exposure to thymidine analogs and/or ddI, without exposure, and uninfected controls and the association with cardiovascular disease risk factors.Methods:In all, 761 PLWH from the Copenhagen Comorbidity in HIV Infection study, and 2283 age and sex-matched uninfected controls from the Copenhagen General Population Study were included. PLWH were stratified according to prior exposure to thymidine analogs and/or ddI. VAT and SAT were determined by abdominal computed tomography scan. Hypotheses were tested using regression analyses.Results:Exposure to thymidine analogs and/or ddI was associated with 21.6cm2 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 thymidine analogs and/or ddI [3.7cm2 per year (2.3-5.1)], but not time since discontinuation [-1.1cm2 per year (-3.4 to 1.1)], was associated with VAT. Prior exposure to thymidine analogs and/or ddI was associated with excess risk of hypertension [adjusted odds ratio (aOR) 1.62 (1.13-2.31)], hypercholesterolemia [aOR 1.49 (1.06-2.11)], and low high-density lipoprotein [aOR 1.40 (0.99-1.99)].Conclusions:This study suggests a potentially irreversible and harmful association of thymidine analogs and ddI with VAT accumulation, which appears be involved in the increased risk of hypertension, hypercholesterolemia, and low high-density lipoprotein found in PLWH with prior exposure to thymidine analogs and/or ddI, even years after treatment discontinuation.

AB - Background:Thymidine analogs and didanosine (ddI) have been associated with redistribution of body fat from subcutaneous adipose tissue (SAT) to visceral adipose tissue (VAT), which, in turn, is a risk factor for cardiovascular disease. We explored differences in adipose tissue distribution between people living with HIV (PLWH) with prior exposure to thymidine analogs and/or ddI, without exposure, and uninfected controls and the association with cardiovascular disease risk factors.Methods:In all, 761 PLWH from the Copenhagen Comorbidity in HIV Infection study, and 2283 age and sex-matched uninfected controls from the Copenhagen General Population Study were included. PLWH were stratified according to prior exposure to thymidine analogs and/or ddI. VAT and SAT were determined by abdominal computed tomography scan. Hypotheses were tested using regression analyses.Results:Exposure to thymidine analogs and/or ddI was associated with 21.6cm2 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 thymidine analogs and/or ddI [3.7cm2 per year (2.3-5.1)], but not time since discontinuation [-1.1cm2 per year (-3.4 to 1.1)], was associated with VAT. Prior exposure to thymidine analogs and/or ddI was associated with excess risk of hypertension [adjusted odds ratio (aOR) 1.62 (1.13-2.31)], hypercholesterolemia [aOR 1.49 (1.06-2.11)], and low high-density lipoprotein [aOR 1.40 (0.99-1.99)].Conclusions:This study suggests a potentially irreversible and harmful association of thymidine analogs and ddI with VAT accumulation, which appears be involved in the increased risk of hypertension, hypercholesterolemia, and low high-density lipoprotein found in PLWH with prior exposure to thymidine analogs and/or ddI, even years after treatment discontinuation.

U2 - 10.1097/QAD.0000000000002119

DO - 10.1097/QAD.0000000000002119

M3 - Journal article

C2 - 30585844

SN - 0269-9370

VL - 33

SP - 675

EP - 683

JO - AIDS

JF - AIDS

IS - 4

ER -

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

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