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LONG-LASTING ALTERATIONS IN FAT DISTRIBUTION IN PLWH EXPOSED TO THYMIDINE ANALOGUES
Marco Gelpi1, Shoaib Afzal2, Andreas Fuchs1, Jens D. Lundgren1, Andreas D. Knudsen1, Ninna Drivsholm1, Anne-Mette Lebech1, Birgitte Lindegaard1, Jørgen T. Kuhl1, Per E. Sigvardsen1, Lars Køber1, Børge Nordestgaard3, Klaus F. Kofoed1, Susanne D. Nielsen1
1Rigshospitalet, Copenhagen, Denmark,2Herlev and Gentofte Hospital, Copenhagen, Denmark,3University of Copenhagen, Copenhagen, Denmark
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/without prior exposure to TA and/or ddI and uninfected controls and the association with CVD risk factors.
761 PLWH from the COCOMO study aged > 40 and 2,283 age- and sex-matched uninfected controls from the GCPS 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 by linear and logistic regression analyses adjusted for age, sex, origin, smoking, physical activity, and BMI.
Age and sex distribution were similar in PLWH and uninfected controls (54.2 vs 54.4 years and 85.5% vs 85.5% male). 451 (60.5%) PLWH had exposure to TA and/or ddI. Of those, 6 (1.4%) were still exposed. Mean cumulative exposure was 6.6 (SD, 4.2) years and time since discontinuation was 9.4 (SD, 2.7) years. After adjustment, prior exposure to TA and/or ddI was associated with 21.6 cm2 larger VAT (13.8 –29.3) compared to HIV infection without exposure and HIV-negative status was associated with similar VAT compared to HIV infection without exposure (Table 1). After adjustment, HIV infection with exposure to TA and/or ddI was associated with 14.8 cm2 smaller SAT compared to HIV infection without (-23.3 - -6.3) (Table 1). HIV-negative status was associated with 13.0 cm2 larger SAT compared to HIV infection without exposure (5.8 - 20.3) (Table 1). Cumulative exposure to TA and/or ddI (3.7 cm2 per year [2.3 - 5.1]), but not time since discontinuation (-1.1 cm2 per year [-3.4 – 1.1]), was associated with VAT. In PLWH, after adjusting for confounders 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]).
Prior exposure to TA and/or ddI was associated with long-lasting alterations in abdominal fat distribution, persisting after TA and/or ddI discontinuation, which may be involved in the excess risk of hypertension, hypercholesterolemia, and low HDL found in PLWH with prior exposure to TA and/or ddI. Our findings may help to identify a subgroup of PLWH who may benefit from more intensive monitoring and cardiovascular prevention interventions.