Use of edoxaban for the treatment of venous thromboembolism in HIV-infected patients.

Abstract

Recent evidence suggests that HIV may be involved in a major incidence of venous thromboembolism related both to HIV pro-inflammatory changes and to viral affection of haematological system 1. Direct oral anticoagulants (DOACs) have changed the treatment of thromboembolic disease; however, co-administration with highly active antiretroviral therapy (HAART) should be considered with caution, because of potential drug–drug interactions 2. Herein we report three cases of HIV-infected patients successfully treated with edoxaban while on HAART. The first case is that of a 63-year-old man who started HAART with emtricitabine/rilpivirine (as hydrochloride)/tenofovir disoproxil 10 years ago and who achieved undetectable HIV RNA. He had been on vitamin K antagonist (VKA) treatment since January 2010 because of three episodes of deep vein thrombosis (DVT) of the lower limbs. In October 2018, after the occurrence of a new DVT, we decided to switch the patient to DOAC edoxaban 30 mg (the patient's weight was 55 kg). The second case is that of a 62-year-old man who had been on HAART consisting of emtricitabine/tenofovir disoproxil and raltegravir for 10 years. In November 2018, edoxaban 60 mg was started for acute DVT and stopped after 6 months because of the resolution of thrombosis. The third case is that of a 60-year-old man who was diagnosed with HIV infection, pulmonary embolism and DVT of the lower limbs in November 2018 during hospitalization for pneumonia caused by Pneumocystiis carinii. He started HAART consisting of emtricitabine/tenofovir disoproxil and dolutegravir and low-molecular-weight heparine (LMWH). Edoxaban 60 mg was started after discharge. The three patients were checked for blood count and renal and liver function after the first month and every 3 months during edoxaban therapy: the results were all within the normal ranges. HIV RNA levels remained undetectable in the first two patients who had been on HAART for many years before the start of edoxaban treatment; in the third patient, we documented an increase in the CD4 count and a decrease in HIV RNA, indicating that HAART was effective. Edoxaban levels measured with an anti- Factor X activated chromogenic assay were in the expected therapeutic range (10–39 ng/mL) 3: 33 ng/mL for patient 1, 24 ng/mL for patient 2 and 10 ng/mL for patient 3. The patients did not report any haemorrhagic or thrombotic adverse events during the clinical follow-up, the duration of which was 10 months for patient 1, 6 months for patient 2 and 7 months for patient 3. Other reports in the literature on the use of the DOACs dabigatran, apixaban and rivaroxaban in HIV-infected patients during ART have confirmed their safety profiles, although dose adjustment is required to account for the likelihood of increased bioavailability of the anticoagulants 4. Edoxaban is minimally metabolized by Cytochrome P450 3A4 (< 10%) and is transported via P-glycoprotein (P-gp) 5. Our patients were on HAART with drugs that are metabolized predominantly by cytochrome P450 and that do not affect the P-gp pathways, so edoxaban dose reduction was unnecessary and co-administration was safe at the full dose . Our experience with edoxaban suggests that it is important to evaluate drug pharmacokinetics for potential drug–drug interactions with the aim of choosing the best DOAC therapy for each patient.