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ANTIRETROVIRAL DRUGS ASSOCIATED WITH SUBCLINICAL CORONARY ARTERY DISEASE
Helen Kovari1, Alexandra Calmy2, Thanh Doco-Lecompte2, René Nkoulou2, Alex Marzel1, Rainer Weber1, Philipp A. Kaufmann1, Ronny R. Buechel1, Bruno Ledergerber1, Philip E. Tarr3
1University Hospital Zurich, Zurich, Switzerland,2University Hospitals of Geneva, Geneva, Switzerland,3University of Basel, Basel, Switzerland
Definite and validated coronary artery disease (CAD) events have been associated with certain antiretroviral therapy (ART) agents. In contrast, the influence of ART drugs on early, subclinical atherosclerosis as determined by coronary artery calcium (CAC) scoring and coronary CT angiography (CCTA) is yet to be elucidated.
In this prospective study of ≥45 year old Swiss HIV Cohort Study participants, CAC scoring and CCTA were performed. The following subclinical CAD endpoints were analysed separately: CAC score >0, any plaque, calcified plaque, and non-calcified/mixed plaque on CCTA. Logistic regression was used to explore associations between the different CAD endpoints and cumulative exposure to ART, ART classes, and the ten most often used individual drugs. Covariables included sex, age, smoking, hypertension, dyslipidemia, diabetes, CD4 nadir <50 cells/µL, and peak HIV-1 RNA >100'000 copies/mL.
We included 428 participants (mean age 52 years, 86% men, 91% Caucasian, 35% current smokers, 60% homosexual, median CD4 cell count at cardiac imaging 598 cells/μL, 93% on ART, 87% with undetectable HIV-1 RNA). CAC score >0 was recorded in 227 (53%) patients, any plaque in 226 (53%), calcified plaque in 158 (37%), and non-calcified/mixed plaque in 158 (37%) participants, respectively. Cumulative exposure to PIs was associated with calcified plaque (adjusted odds ratio (aOR) per 5 years 1.21 [95% confidence interval, 1.01-1.46]). The associations between cumulative exposure to individual ART drugs and different CAD outcomes are shown in the figure. Adjustment for covariables did only marginally affect point estimates. CAC score >0 was not associated with any individual ART drug. Any plaque was associated with cumulative exposure to regimens containing atazanavir (aOR per 5 years 1.66 [1.11-2.47]), and abacavir (1.38 [1.03-1.85]). Calcified plaque was associated with exposure to atazanavir (1.47 [1.01-2.14]). Non-calcified/mixed plaque was associated with exposure to abacavir (1.45 [1.10-1.91]).
We found an increased risk of coronary artery plaque in patients exposed to regimens containing atazanavir or abacavir independent of CAD risk factors. Atazanavir was associated with calcified plaque whereas abacavir was associated with non-calcified/mixed plaques. Although adjustment for traditional cardiovascular risk factors only marginally affected associations with individual drugs, we cannot fully exclude residual confounding.