Impact of a factor Xa inhibitor (apixaban) on SIV pathogenesis and response to antiretroviral therapy

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Abstract

Antiretroviral therapy (ART) has prolonged the life expectancy of persons living with HIV, the majority of whom are now older than 50 years. Aging people with HIV are at increased risk for cardiovascular events driven by HIV-related inflammation and hypercoagulation. Apixaban is a factor Xa inhibitor that reduces cardiovascular risks and treats stroke, deep vein thrombosis, and pulmonary embolism. We assessed apixaban’s impact on key parameters of HIV/SIV pathogenesis in SIV-infected, aged rhesus macaques (RMs) receiving ART. Inflammation, coagulation, T cell subsets, B cells, and macrophages and their immune activation status were monitored throughout the study. We found no significant differences between the apixaban-treated and control groups for virus replication or CD4+ T cell recovery in blood and tissues after ART. Apixaban did not significantly affect D-dimer, immune activation, or inflammation of SIV-infected, ART-treated RMs. Apixaban-treated RMs experienced multiple bleeding episodes, tissue hemorrhages, and myocardial infarctions, as demonstrated by pathological examination of necropsy-collected tissues. Given apixaban’s lack of effect on immune activation, CD4+ T cell restoration, and inflammation, along with increased risk of hemorrhage, factor Xa inhibition may not be an efficient or safe option to target and prevent cardiovascular events in aging people with HIV.

Authors

Cuiling Xu, Haritha Annapureddy, Lilly Carson, Vansh Khurana, Ranjit Sivanandham, Sindhuja Sivanandham, Tianyu He, Kevin D. Raehtz, Janet Kim, Christie Biber, Norma Arbujas-Silva, Mohammed Daira, Sudhapriya Kandasamy, Matthew J. Feinstein, Irini Sereti, Cristian Apetrei, Ivona Pandrea