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

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 -