2148. Lack of Interaction Between Elbasvir/Grazoprevir and Approved HIV and HBV Drugs in Viral Replication In Vitro.
Session: Poster Abstract Session: HIV/HCV Coinfection and Liver Disease
Saturday, October 29, 2016
Room: Poster Hall
Background: Approximately 25% of Human Immunodeficiency Virus (HIV) patients in the U.S. are co-infected with Hepatitis C Virus (HCV). Among chronic Hepatitis B virus patients, HCV co-infection rates vary from 9 to 30% worldwide. The combined treatment of HIV or HBV with HCV infections can be complicated by drug-drug interactions. Grazoprevir (GZR), an NS3/4A protease inhibitor, and elbasvir (EBR), an NS5A replicase inhibitor, were co-developed to treat chronic HCV infection. We performed in vitro studies to measure antiviral activities of GZR or EBR independently and in combination with representatives of approved HIV and HBV drugs.

Methods: GZR and EBR were tested in combination with two approved representatives of HIV drugs: NRTI (tenofovir and emtricitabine), NNRTI (efavirenz and rilpivirine), Integrase (raltegravir and dolutegravir), Protease (atazanavir and darunavir), and Entry (maraviroc and enfuvirtide). Lamivudine was used for HBV testing. HIV and HBV drugs were tested at Cmin, Cmax, and 3X Cmaxof 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 the HIV drugs were determined in MT4_GFP Jurkat cell lines expressing green fluorescence protein (GFP) that 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: The presence of the HIV or HBV drugs did not impact the inhibitory potencies of GZR or EBR in HCV replication. Conversely, the antiviral activities of representatives of approved HIV drugs were evaluated in HIV replication. The presence of GZR did not change the EC50 values for the HIV drugs tested with one exception (the presence of 100 nM GZR increased modestly the EC50of maraviroc from 0.38 to 0.45 nM (p value = 0.03)). The presence of EBR did not change the inhibitory potencies of any of the HIV drugs tested.

Conclusion: The HIV and HBV drugs tested did not impact the antiviral activity of either GZR or EBR. Conversely, neither GZR nor EBR meaningfully affected the antiviral activity of the HIV and HBV compounds in HIV and HBV replication, respectively.

Robert Chase, MA1, Stephanie Curry, MS1, Min Xu, PhD2, Lei Ba, MS2, Carolyn Bahnck-Teets, MS2, Frederick Lahser, PhD1, Steve Carroll, PhD2 and Ernest Asante-Appiah, PhD1, (1)Infectious Disease, Merck, Kenilworth, NJ, (2)Pharmacology, Merck, West Point, PA

Disclosures:

R. Chase, Merck: Employee , Salary

S. Curry, Merck: Employee , Salary

M. Xu, Merck: Employee , Salary

L. Ba, Merck: Employee , Salary

C. Bahnck-Teets, Merck: Employee , Salary

F. Lahser, Merck: Employee , Salary

S. Carroll, Merck: Employee , Salary

E. Asante-Appiah, Merck: Employee , Salary

Findings in the abstracts are embargoed until 12:01 a.m. CDT, Wednesday Oct. 26th with the exception of research findings presented at the IDWeek press conferences.