Direct oral anticoagulants for the management of venous thromboembolism in patients with HIV – a single centre experience

Ricardo Oliveira, Raj K. Patel, Chris Taylor, Julia Czuprynska, Roopen Arya, Lara N. Roberts

Human immunodeficiency virus (HIV) infection remains one of the biggest health burdens worldwide, affecting 36.9 million people (World Health Organisation, 2017). Venous thromboembolism (VTE) has a reported incidence of 0.19–7.63% in those with HIV, representing a 2–10 fold increase compared to the general population (Bibas et al, 2011;

Rasmussen et al, 2011). The seminal studies of direct oral anticoagulants (DOACs) in VTE did not report outcomes specifically for patients with HIV, and those on potentially interacting antiretroviral therapy (ART) were excluded from studies of direct factor Xa (Fxa) inhibitors (Schulman et al, 2009; EINSTEIN Investigators, 2010; Agnelli et al, 2013; The HOKUSAI‐VTE Investigators, 2013). Thus there is very little published regarding the use of DOACs in this population. Consequently, VTE in these patients continues to be predominantly managed with low molecular weight heparin (LMWH) followed by vitamin K antagonists (VKA).

The main limiting factor for the use of FXa inhibitors in this population is the potential interaction with the ART due to inhibition/induction of the cytocrome P450 3A4 leading to a respective increase or decrease in DOAC concentration (Egan et al, 2014). In contrast, dabigtran is predominantly renally excreted; however its prodrug dabigatran etexilate is a substrate for PgP glycoprotein, which is inhibited by protease inhibitors (PI; Egan et al, 2014). Concurrent administration of PI and dabigatran results in a significant increase in dabigatran bioavailability. This effect can be minimised by dose spacing of dabigatran two hours prior to PI administration (Egan et al, 2014). Thus of the four licenced DOACs, dabigatran has the least interaction with ART.