VTE and HIV

Venous thromboembolism (VTE ) risk is increased in HIV patients (5.7 -11.00/1000 person years) compared to the general population (1.0/1000 person years, with all data predating 2003. C. Rokx et al aimed to look at VTE in the current era in the Dutch Athena cohort with data between 2003-2014 on 14,386 patients.202/229 first VTE occurred in proximal leg veins or pulmonary arteries and 153/202 had withdrawn anticoagulants. 32 recurrent VTE occurred (59 VTE/1000person years; 95% CI; 41-83). Kaplan-Meier recurrence rates at 1, 2 and 5 years of follow-up were 16% 19% and 28% following unprovoked first VTE. When CD4 cell count is above 500, VTE incidence approaches that of the general population. Conclusion: Patients with persistent low CD4 cell counts might benefit from longer anticoagulant therapy. C Rokx et al, CROI 2017 Abstract #620.

I have seen a number of HIV patients with VTE over the years, the last being 2 months ago with the major concern at the time being a potential drug-drug interaction.  So, what new information was available at CROI regarding that drug-drug interaction?

As you are all aware, Ritonavir (RTV) and cobicistat (COBI) are antiretroviral pharmacokinetic (PK) enhancers that can inhibit several drug transporters, including P-glycoprotein (P-gp) and renal multidrug and toxin extrusion-1 (MATE-1). Dabigatran etexilate DE (trade name Predaxa) is the prodrug form of the oral direct thrombin inhibitor, dabigatran, and is a substrate for these transporters. Kristina M. Brooks and colleagues conducted a single centre open-label fixed sequence PK study on 16 healthy volunteers to evaluate the effects of separated and simultaneous administration of RTV and COBI on dabigatran PK. Findings: No significant changes in dabigatran exposure were observed with simultaneous RTV administration, possibly due to mixed induction and inhibition of P-gp by RTV. However, COBI resulted in significant increases in dabigatran exposure that persisted despite separating administration, most likely due to intestinal P-gp inhibition. These findings suggest RTV and DE can likely be co-administered, whereas the use of DE and COBI may require reduced dosing and careful clinical monitoring. K. Brooks et al CROI 2017 # 409. My patient is continuing to do well on Dibigatran (normal dose) and Genvoya. We will see Dabigatran used more often in HIV patients with thrombo-embolic disease.