Antiviral Activity of Elbasvir/Grazoprevir Unaffected by HIV/HBV Drugs
NEW ORLEANS, LA—HIV and hepatitis B virus (HBV) drugs had no impact on antiviral activity of grazoprevir or elbasvir, and neither agent affected HIV and HBV replication, a study presented at IDWeek has shown.
Approximately 25% of U.S. patients with HIV are co-infected with hepatitis C virus (HCV) and, among patients with chronic HBV, HCV co-infection rates vary from 9 to 30% worldwide. Co-infection with HIV or HBV raises the risk of liver diseases and liver failure, and liver-related death from HCV.
The combined treatment of HIV or HBV with HCV infections can be complicated by drug-drug interactions, higher pill burden, and toxicities, noted Robert Chase, MA, Infectious Disease, Merck, Kenilworth, NJ.
Grazoprevir, an NS3/4A protease inhibitor, and elbasvir, an NS5A replicase inhibitor, were co-developed to treat chronic HCV infection. The study sought to measure the antiviral activities of these agents both independently and in combination with representatives of approved HIV and HBV drugs in vitro. The HIV regimens were NRTI (tenofovir and emtricitabine), NNRTI (efavirenz and rilpivirine), integrase strand inhibitors (raltegravir and dolutegravir), protease inhibitors (atazanavir and darunavir), and entry inhibitors (maraviroc and enfuvirtide), and the HBV agent tested was lamivudine.
HIV drugs were tested at 0.3X Cmin, Cmax, and 3X Cmax of their human plasma levels; lamivudine was tested at 0.2X Cmin, Cmax, and 5X Cmax of their human plasma levels. HCV cell-based assays were conducted in stable GT1a replicon Huh7 cell lines treated with various inhibitor concentrations for 72 hours to determine potencies by qRT-PCR.
Inhibitory potencies for HIV drugs were determined in MT4_GFP Jurkat cell lines expressing green fluorescence protein, which is dependent on HIV-1 tat and rev proteins. HBV combination assays were performed in HepG2.2.15 cell lines using real-time qPCR readout of HBV copy number.
Results showed that “the presence of the HIV or HBV drugs did not impact the inhibitory potencies of grazoprevir or elbasvir in HCV replication,” the investigators reported. “Conversely, the antiviral activities of representatives of approved HIV drugs were evaluated in HIV replication.”
Grazoprevir did not change EC50 values for the HIV drugs tested, with one exception: 100nM grazoprevir increased the EC50 of maraviroc from 0.38 to 0.45nM (P=0.03). The presence of elbasvir did not change inhibitory potencies of any HIV drug tested.