Co-infection Model and Drug Treatment: Human PBMCs were isolated from blood of three HIV-1 negative healthy donors, activated and co-cultured with Huh7 cells. Cells were exposed to a) 1 ng of p24 JR-CSF alone (HIV-1-infected PBMCs + uninfected Huh7 cells) or b) 1 ng of p24 JR-CSF together with 100 ng JFH-1 (HIV-1-infected

PBMCs + HCV-Huh7 cells) and cultured for 2 weeks. Cells were treated with 2 each of DMSO, nelfinavir, CPI-431-32 or daclatasvir either 3 hours before or 3 days after exposure to HIV-1/HCV. Viral replication was monitored every 3 days for 15 days by measuring amounts of HIV-1 capsid and HCV core proteins in the cell culture supernatants by HIV-1 p24 NVP-AUY922 research buy and HCV core ELISA. RESULTS:

Treatment of co-infected human LDE225 cells with CPI-431-32 fully prevented HCV and HIV-1 viral replication when added prior to viral exposure. CPI-431-32 also inhibited HCV and HIV-1 viral replication when added 3 days after viral exposure. In co-infected cells, CPI-431-32 and nelfinavir, but not daclatasvir, reduced levels of HIV-1 capsid protein to undetectable levels. CPI-431-32 and daclatasvir, but not nelfinavir, reduced HCV core protein to undetectable levels. CONCLUSIONS: We developed a unique in vitro co-infection model to test candidate drugs for the treatment of patients co-infected with HCV/ HIV-1. CPI-431-32 is a candidate medicine for the treatment of HCV/HIV-1 co-infection. Based on the results of our study, we believe that CPI-431-32 has the potential, as a single agent or

in combination with DAAs, to inhibit both HCV and HIV-1 viral infections. Further evaluation of CPI-431-32 in preparation for clinical testing is warranted. Disclosures: Dan Trepanier – Employment: Ciclofilin Pharmaceuticals Daren Ure – Employment: Ciclofilin Pharmaceuticals Megestrol Acetate Cosme Ordonez – Management Position: Ciclofilin Pharmaceuticals Robert T. Foster – Management Position: Ciclofilin Pharmaceuticals Inc. The following people have nothing to disclose: Philippe Gallay, Michael Bobardt Objective: HCV genotype 4 (GT4) infection is prevalent in the Middle East and North and sub-Saharan Africa and emerging in Europe. The PEARL-I study assessed safety and efficacy of an oral, interferon-free regimen of ombitasvir (an NS5A inhibitor) and ABT-450 (an NS3/4A protease inhibitor identified by AbbVie and Enanta) plus ritonavir (ABT-450/r) with/ without ribavirin (RBV) in treatment-naTve (TN) and peginter-feron/RBV-experienced noncirrhotic patients with HCV GT1b and GT4 infection. Here we report results from the cohorts of HCV GT4-infected patients. Methods: TN patients received once-daily ombitasvir 25 mg and ABT-450/r 150/100 mg with/without weight-based twice-daily RBV for 12 weeks; treatment-experienced (TE) patients received the RBV-containing regimen.