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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

Gelpi, M; Afzal, S; Fuchs, A; Lundgren, J; Knudsen, AD; Drivsholm, N; Mocroft, A; ... Nielsen, SD; + view all (2019) Prior exposure to thymidine analogues and didanosine is associated with long-lasting alterations in adipose tissue distribution and cardiovascular risk factors. AIDS , 33 (4) pp. 675-683. 10.1097/QAD.0000000000002119. Green open access

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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.

Type: Article
Title: Prior exposure to thymidine analogues and didanosine is associated with long-lasting alterations in adipose tissue distribution and cardiovascular risk factors
Open access status: An open access version is available from UCL Discovery
DOI: 10.1097/QAD.0000000000002119
Publisher version: https://doi.org/10.1097/QAD.0000000000002119
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: fat redistribution; cardiovascular risk factors; thymidine analogues; didanosine; visceral adipose tissue
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health
URI: https://discovery.ucl.ac.uk/id/eprint/10065149
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