Boceprevir in combination with HIV protease inhibitors in patients with advanced fibrosis‐altered drug‐drug interactions?

Abstract

In HIV/HCV co‐infected patients improved treatment outcomes have been reported for the HCV protease inhibitors (PIs) boceprevir (BOC) and telaprevir (TVR), reaching SVR rates of up to 70% in pilot trials. Due to complex drug‐drug‐interactions triple therapy is substantially limited in HIV/HCV‐coinfected individuals. Co‐administration of BOC with the commonly available HIV PIs has been reported not only to decrease the level of BOC but also to lead to relevant decreases in the respective HIV PI. Here, we report on two patients who received BOC‐containing HCV triple therapy in combination with a HIV PI. Patient 1 was on darunavir 800 mg/ritonavir 100 mg once‐daily mono‐therapy. Using FibroScan a liver stiffness of 34 kPa suggested liver cirrhosis prior to start of HCV triple therapy. At week 5 of HCV triple therapy darunavir trough concentration was measured in the reference range with 3777 ng/ml (reference trough concentration 2400–4600 ng/ml). HCV‐RNA became negative at week 10 and HIV‐RNA was below detection limit (<40 copies/ml) at all times. Patient 2 was on a simplified FTC qd and fos‐amprenavir 700 mg/ritonavir 100 mg bid regimen. Liver disease had also progressed to liver cirrhosis, confirmed in FibroScan, with a liver stiffness of 32 kPa. At week 8 of HCV triple therapy fos‐amprenavir trough level was measured in the normal reference range with 1699 ng/ml (reference trough concentration 750–2500 ng/ml). At week 11 HCV‐RNA was <12 IU/ml and HIV viral load was below detection limit of <40 copies/ml at all times. Our clinical data suggest that in patients with advanced liver disease possibly drug levels of HIV PIs which are coadministered with BOC may be within the normal range. In order to better understand the true amount of drug interactions between BOC and commonly used HIV PIs in HIV/HCV‐coinfected patients with more advanced liver fibrosis, urgently more PK studies are required to make HCV triple therapy accessible for a wider number of HIV/HCV‐coinfected patients in desperate need of these drugs.