Utilization of Direct Oral Anticoagulants in People Living with Human Immunodeficiency Virus: Observational Data from the District of Columbia Cohort

Abstract

Background: Direct oral anticoagulants (DOACs) have become first-line treatment for venous thrombotic events. DOAC prescribing trends among people living with human immunodeficiency virus (PWH) are not well described. The coadministration of DOACs with the antiretroviral (ARV) pharmacokinetic boosters ritonavir (RTV) or cobicistat (COBI) may be complicated by pharmacokinetic interactions.

Methods: A longitudinal cohort study was conducted using the D.C. Cohort Database in Washington, D.C., from January 2011 to March 2017, to describe oral anticoagulant prescribing among PWH ≥ 18 years old and the prevalence of DOAC use with RTV or COBI. Data collection included demographic and clinical characteristics, ARV and anticoagulant prescriptions, and International Classification of Diseases Ninth and Tenth Edition diagnosis codes.

Results: Among 8315 PWH, there were 236 anticoagulant prescriptions (96 DOAC, 140 warfarin) for 206 persons. PWH prescribed anticoagulants were predominantly Black (82%) and male (82%), with a mean age at anticoagulant initiation of 56 years. DOAC use increased from 3% of total anticoagulant prescribing in 2011 to 43% in 2016, accounting for 64% of all newly recorded anticoagulant prescriptions by 2016. There were 19 bleeding events recorded among 16 individuals. Despite the Food and Drug Administration label recommendation to avoid rivaroxaban with boosted ARVs, 41% remained on boosted ARVs after rivaroxaban initiation.

Conclusions: DOAC use increased substantially in PWH by 2016. Although rivaroxaban is not recommended with RTV or COBI, concomitant use was recorded in 41% of rivaroxaban recipients in this cohort. As DOAC usage increases, clinicians need to be aware of potential DOAC/ARV interactions in order to select the most appropriate oral anticoagulant and monitoring plan for PWH.

Keywords: HIV; anticoagulation; antiretrovirals; cobicistat; ritonavir.

Figure 1.

A, Trends in overall oral anticoagulant prescriptions in the D.C. Cohort, by drug, 2011–2016, where n is the total number of prescriptions in a given year. Differences in the proportion of warfarin and total DOAC by year were analyzed using a Fisher Chi-square test (<.0001). Using a stratified Poisson regression, there were significant increases in the counts of DOAC (P < .0001) and warfarin (P < .0001) over time. B, Newly recorded oral anticoagulant prescriptions in the D.C. Cohort, by drug and year, 2011–16, where n is the number of newly recorded prescriptions in a given year. Differences in the proportion of warfarin and total DOAC by year were analyzed using a Fisher Chi-square test (<.0001). Using a stratified Poisson regression, there was a significant increase in the count of DOAC (P < .0001), but not in warfarin (P = .15) over time. Abbreviation: D.C., District of Columbia; DOAC, direct oral anticoagulants.

Figure 2.

Boosted ART prescribing patterns before and 1 month after anticoagulant initiation. Changes in ART prescribing were assessed at 1 month postanticoagulant initiation. These changes were consistent at 6 months postanticoagulation. Dosing adjustments for concomitant ART could not be evaluated for dabigatran, apixaban, or warfarin. There were no statistically significant differences between the DOAC and warfarin groups (P > .05; Fisher Chi-square). Boosted regimens include atazanavir/cobicistat, cobicistat, darunavir/cobicistat, darunavir/cobicistat/tenofovir alafenamide/emtricitabine, elvitegravir/cobicistat/tenofovir alafenamide/emtricitabine, elvitegravir/cobicistat/tenofovir disoproxil fumarate/emtricitabine, lopinavir/ritonavir, and ritonavir. Abbreviations: ART, antiretroviral therapy; COBI, cobicistat; DOAC, direct oral anticoagulants; RTV, ritonavir.