Secondary Logo

Journal Logo

Institutional members access full text with Ovid®

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

Gelpi, Marcoa; Afzal, Shoaibb; Fuchs, Andreasc; Lundgren, Jensa,d; Knudsen, Andreas D.a; Drivsholm, Ninnaa; Mocroft, Amandae; Lebech, Anne-Mettea; Lindegaard, Birgittef,g; Kühl, Jørgen T.c; Sigvardsen, Per E.c; Køber, Larsc; Nordestgaard, Børge G.b,h; Kofoed, Klaus F.c,i; Nielsen, Susanne D.a

doi: 10.1097/QAD.0000000000002119
CLINICAL SCIENCE
Buy
SDC

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 cm2 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 cm2 per year (2.3–5.1)], but not time since discontinuation [−1.1 cm2 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.

aViro-immunology Research Unit, Department of Infectious Diseases 8632, Rigshospitalet, University of Copenhagen, Copenhagen

bThe Copenhagen General Population Study, Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev

cDepartment of Cardiology, Rigshospitalet

dCHIP, Department of Infectious Diseases 8632, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

eHIV Epidemiology and Biostatistics Unit, Department of Infection and Population Health, UCL, London, UK

fCenter for inflammation and Metabolism, Rigshospitalet

gDepartment of Pulmonary and Infectious Diseases, Nordsjællands Hospital, Hillerød

hFaculty of Health and Medical Scienses, University of Copenhagen

iDepartment of Radiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; On behalf of the Copenhagen Comorbidity in HIV Infection (COCOMO) Study, Denmark.

Correspondence to Susanne D. Nielsen, MD, DMSc, Associate Professor, Viro-immunology Research Unit, Department of Infectious Diseases 8632, Copenhagen University Hospital, Blegdamsvej 9B, DK-2100 Copenhagen Ø, Denmark. Tel: +45 3545 0859; fax: +45 3545 6648; e-mail: sdn@dadlnet.dk

Received 1 October, 2018

Revised 19 November, 2018

Accepted 29 November, 2018

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com).

Copyright © 2019 Wolters Kluwer Health, Inc.