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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Prior exposure to thymidine analogs and didanosine is associated with long-lasting alterations in adipose tissue distribution and cardiovascular risk factors. / Gelpi, Marco; Afzal, Shoaib; Fuchs, Andreas; Lundgren, Jens; Knudsen, Andreas D; Drivsholm, Ninna; Mocroft, Amanda; Lebech, Anne-Mette; Lindegaard, Birgitte; Kühl, Jørgen T.; Sigvardsen, Per E.; Køber, Lars; Nordestgaard, Børge G.; Kofoed, Klaus F.; Nielsen, Susanne D.
I: AIDS, Bind 33, Nr. 4, 2019, s. 675-683.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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
Y1 - 2019
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 21.6 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 thymidine analogs and/or ddI [3.7 cm per year (2.3-5.1)], but not time since discontinuation [-1.1 cm 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 21.6 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 thymidine analogs and/or ddI [3.7 cm per year (2.3-5.1)], but not time since discontinuation [-1.1 cm 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
VL - 33
SP - 675
EP - 683
JO - AIDS
JF - AIDS
SN - 1350-2840
IS - 4
ER -
ID: 224600054