title: Gold drug auranofin restricts the viral reservoir in the monkey AIDS model and induces containment of viral load following ART suspension.
abstract: OBJECTIVE
  A small pool of long-lived memory CD4 T cells harboring the retroviral genome is one main obstacle to HIV eradication. We tested the impact of the gold compound, auranofin, on phenotype and viability of CD4 T cells in vitro, and on persistence of lentiviral reservoir cells in vivo.
  
  
  METHODS
  In-vitro and in-vivo study. The pro-differentiating effect of auranofin was investigated in human primary CD4 T cells, and its capacity to deplete the viral DNA (vDNA) reservoir was tested in a pilot study involving six SIVmac251-infected macaques with viral loads stably suppressed by antiretroviral therapy (ART) (tenofovir/emtricitabine/raltegravir). The study was then amplified by intensifying ART using darunavir/r and including controls under intensified ART alone. All therapies were eventually suspended and viro-immunological parameters were monitored over time.
  
  
  METHODS
  Cell subpopulations were quantitated by flow cytometry following proper hematological analyses. Viral load and cell-associated vDNA were quantitated by Taqman real-time PCR.
  
  
  RESULTS
  In naïve, central memory and transitional memory CD4 T cells, auranofin induced both phenotype changes and cell death which were more pronounced in the memory compartment. In the pilot study in vivo, auranofin transiently decreased the cell-associated vDNA reservoir in peripheral blood. When ART was intensified, a sustained decrease in vDNA was observed only in auranofin-treated monkeys but not in controls treated with intensified ART alone. After therapy suspension, only monkeys that had received auranofin showed a deferred and subsequently blunted viral load rebound.
  
  
  CONCLUSIONS
  These findings represent a first step towards a remission of primate lentiviral infections.
authors.affiliation: BIOQUAL, Inc., Rockville, Maryland, USA.
authors.forename: Mark G
authors.initials: MG
authors.lastname: Lewis
authors.forename: Sandrina
authors.initials: S
authors.lastname: DaFonseca
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chomont
authors.forename: Anna T
authors.initials: AT
authors.lastname: Palamara
authors.forename: Maria
authors.initials: M
authors.lastname: Tardugno
authors.forename: Antonello
authors.initials: A
authors.lastname: Mai
authors.forename: Matt
authors.initials: M
authors.lastname: Collins
authors.forename: Wendeline L
authors.initials: WL
authors.lastname: Wagner
authors.forename: Jake
authors.initials: J
authors.lastname: Yalley-Ogunro
authors.forename: Jack
authors.initials: J
authors.lastname: Greenhouse
authors.forename: Barbara
authors.initials: B
authors.lastname: Chirullo
authors.forename: Sandro
authors.initials: S
authors.lastname: Norelli
authors.forename: Enrico
authors.initials: E
authors.lastname: Garaci
authors.forename: Andrea
authors.initials: A
authors.lastname: Savarino
mesh_terms: D000818:Animals; D044966:Anti-Retroviral Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001310:Auranofin / Q000008:administration & dosage / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D004279:DNA, Viral / Q000187:drug effects; D008253:Macaca mulatta; D010865:Pilot Projects; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology; D015302:Simian Immunodeficiency Virus / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D016896:Treatment Outcome; D019562:Viral Load; D017735:Virus Latency / Q000187:drug effects* / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects* / Q000276:immunology
chemical_list: D044966:Anti-Retroviral Agents; D018501:Antirheumatic Agents; D004279:DNA, Viral; D001310:Auranofin