title: Anti-retroviral drugs do not facilitate hepatitis C virus (HCV) infection in vitro.
abstract: An estimated 4 to 5 million people are co-infected with HIV/HCV worldwide. Recently observed outbreaks of acute HCV infection among HIV-positive men who have sex with men (MSM) have been linked to behavioral factors such as high risk sexual practices and recreational drug use. However, at the molecular level, many drugs such as glucocorticoids or cyclosporine A have been found to modulate viral replication. Thus, it is conceivable that drugs used in highly active antiretroviral therapy (HAART) may heighten susceptibility to HCV infection and contribute to the recent outbreaks. We therefore performed a comprehensive screen of antiretroviral drugs covering all available drug classes both individually and in typical combinations used during HAART to probe for direct effects on HCV cell entry, replication, new particle assembly and release. Importantly, no significant enhancement or inhibition of HCV cell entry, replication or new particle production was detected. While raltegravir and ritonavir boosted atazanavir reduce HCV replication, a tenfold reduction of HCVcc entry by the CCR5 antagonist maraviroc was observed. In conclusion, commonly used HAART agents do not specifically enhance HCV replication. Thus recent epidemic outbreaks of acute HCV in HIV-infected MSM are unlikely to be related to enhancing effects of HAART drugs.
authors: Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, Hannover, Germany.
authors: Lisa
authors: L
authors: Sandmann
authors: Matthew
authors: M
authors: Wilson
authors: David
authors: D
authors: Back
authors: Heiner
authors: H
authors: Wedemeyer
authors: Michael P
authors: MP
authors: Manns
authors: Eike
authors: E
authors: Steinmann
authors: Thomas
authors: T
authors: Pietschmann
authors: Thomas
authors: T
authors: von Hahn
authors: Sandra
authors: S
authors: Ciesek
mesh_terms: D044966:Anti-Retroviral Agents / Q000494:pharmacology*; D002460:Cell Line; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology*; D022781:Hepatocytes / Q000187:drug effects / Q000821:virology; D006801:Humans; D019065:Virus Assembly / Q000187:drug effects*; D053586:Virus Internalization / Q000187:drug effects*; D057074:Virus Release / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D044966:Anti-Retroviral Agents