Publication Date:
2016-12-02
Description:
Introduction: Effective treatment of HIV infection with antiretroviral therapy (ART) has prolonged survival and shifted causes of death to non-AIDS defining illnesses such as cardiovascular disease (CVD). Increased thrombin generation is evident from increased D-dimer levels in HIV; previously we have shown that inflammation and viral replication associate with imbalances in pro and anticoagulant factors resulting in increased thrombin generation profiles when mathematically modeled. We explore for the first time the hypothesis that factor compositional imbalance increases simulated thrombin generation and predicts mortality in HIV. Methods: In a nested case-control study of the SMART and ESPRIT participants randomized to continuous ART, we evaluated cases of all-cause mortality and controls (1:3) matched on enrollment date, age (± 5yrs), study, and country. Thrombin generation in response to a 5 pM tissue factor initiator for each individual was calculated by a mathematical model incorporating levels of factors II, V, VII, VIII, IX, X, antithrombin, tissue factor pathway inhibitor and protein C. Thrombin generation metrics included time to clot, maximum rate (MaxR), maximum level (MaxL) and area under the curve (AUC). Conditional logistic regression was used to compare parameters between cases and controls, adjusted for age, gender, and race/ethnicity. Results: Among cases (n=129) and controls (n=369), respectively, median CD4 count was 451 and 496 cells/mm3, and 65 and 77% had HIV viral suppression (
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
