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Longitudinal evaluation of cardiovascular disease-associated biomarkers in relation to abacavir therapy

Hammond, E., McKinnon, E., Mallal, S. and Nolan, D. (2008) Longitudinal evaluation of cardiovascular disease-associated biomarkers in relation to abacavir therapy. In: 10th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV, 6 - 8 November 2008, London, England.


Objectives: data from the D:A:D study indicate that recent use of abacavir, but not stavudine or zidovudine, is associated with increased risk of myocardial infarction (MI). The aim of this study was to evaluate longitudinal biomarkers of cardiovascular relevance in abacavir therapy and test whether risk profiles were higher with abacavir treatment compared with untreaated HIV, or with stavudine or zidovudine treatment.

Methods: Samples were obtained retrospectively from the West Australian HIV observational cohort, and there was no MI in the study population. The longitudinal effect of abacavir treatment was considered in three study groups: (1) antiretroviral therapy (ART)-naive patients initiating abacavir but not stavudine or zidovudine (n=15), (2) previously abacavir-naive patients switching from thymidine nucleoside reverse transcriptase inhibitor (tNRTI) therapy (n=13) or (3) ongoing abacavir use in patients switching tNRTI treatment (n=13).

D-dimer and Hs-CRP were measured by latex immunoiassay and latex-enhanced nephelometry, respectively. All other analytes interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-a, monocyte chemotactic protein (MCP)-1, hepatocyte growth factor (HGF), leptin and adiponectin were determined using the LINCOplex kits (Luminex xMAP Technology). Mixed effects models were used for statistical analyses to accomodate multiple measures per person, with all data log-transformed to satisfy distributional assumptions.

Results: Within 1 year of initiating abacavir from ART-naive baseline, D-dimer levels and CRP were unchanged (P=0.6 and 0.3 respectively), and adiponectine increased (p=0.004). After >1 year from baseline, D-dimer decreased, adiponectin and HGF were unchanged from baseline (P=0.03, 0.9, 0.8, respectively), whereas leptin incresed (P=0.003) and IL-8, TNF and MCP-1 were decreased (all P-values <0.03). IL-6 increased marginally from baseline (P=0.05). The initial rise in adiponectin levels as compared with baseline was not observed in samples beyond 1 year post-initiation of abacavir.

Initiating abacavir after switching from thymidine-based regimens was associated with no changes in the above analytes (all P-values >0.4), except that leptin increased (P=0.002) and TNF marginally increased (P=0.04). Continuing abacavir after switching from thymidines was also associated with no changes in analytes (all P-values >0.1).

Conclusions: No significant change in biomarker profile known to be related to cardiovascular risk was detected in association with abacavir use. In fact, all significant changes from baseline appeared beneficial, possibly attributable to either anti-HIV effects or cessation of thymidines.

Item Type: Conference Item
Murdoch Affiliation(s): Centre for Clinical Immunology and Biomedical Statistics
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