Clinical posts from members and guests of the Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine (ASHM) from various international medical and scientific conferences on HIV, AIDS, viral hepatitis, and sexual health.
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2003-2014 on 14,386 patients.202/229 first VTE occurred in proximal leg veins or pulmonary arteries and 153/202 had withdrawn anticoagulants. 32 recurrent VTE occurred (59 VTE/1000person years; 95% CI; 41-83).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.