title: Investigational treatment suspension and enhanced cell-mediated immunity at rebound followed by drug-free remission of simian AIDS.
abstract: BACKGROUND
  HIV infection persists despite antiretroviral treatment (ART) and is reignited as soon as therapies are suspended. This vicious cycle is fueled by the persistence of viral reservoirs that are invulnerable to standard ART protocols, and thus therapeutic agents able to target these reservoirs are needed. One such agent, auranofin, has recently been shown to decrease the memory T-cell reservoir in chronically SIVmac251-infected macaques. Moreover, auranofin could synergize with a fully suppressive ART protocol and induce a drug-free post-therapy containment of viremia.
  
  
  RESULTS
  We administered buthionine sulfoximine (BSO), an inhibitor of glutathione synthesis currently in clinical trials for cancer, in combination with auranofin to chronically SIVmac251-infected macaques under highly-intensified ART (H-iART). The ART/auranofin/BSO therapeutic protocol was followed, after therapy suspension, by a significant decrease of viral RNA and DNA in peripheral blood as compared to pre-therapy levels. Drug-free post-therapy control of the infection was achieved in animals with pre-therapy viral loads ranging from values comparable to average human set points to levels largely higher. This control was dependent on the presence CD8+ cells and associated with enhanced levels of cell-mediated immune responses.
  
  
  CONCLUSIONS
  The level of post-therapy viral set point reduction achieved in this study is the largest reported so far in chronically SIVmac251-infected macaques and may represent a promising strategy to improve over the current "ART for life" plight.
authors.affiliation: Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161, Rome, Italy.
authors.forename: Iart Luca
authors.initials: IL
authors.lastname: Shytaj
authors.forename: Barbara
authors.initials: B
authors.lastname: Chirullo
authors.forename: Wendeline
authors.initials: W
authors.lastname: Wagner
authors.forename: Maria G
authors.initials: MG
authors.lastname: Ferrari
authors.forename: Rossella
authors.initials: R
authors.lastname: Sgarbanti
authors.forename: Alessandro Della
authors.initials: AD
authors.lastname: Corte
authors.forename: Celia
authors.initials: C
authors.lastname: LaBranche
authors.forename: Lucia
authors.initials: L
authors.lastname: Lopalco
authors.forename: Anna Teresa
authors.initials: AT
authors.lastname: Palamara
authors.forename: David
authors.initials: D
authors.lastname: Montefiori
authors.forename: Mark G
authors.initials: MG
authors.lastname: Lewis
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*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D001310:Auranofin / Q000008:administration & dosage*; D019328:Buthionine Sulfoximine / Q000008:administration & dosage; D004279:DNA, Viral / Q000097:blood; D007111:Immunity, Cellular; D008251:Macaca; D012367:RNA, Viral / Q000097:blood; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000302:isolation & purification; D035703:Therapies, Investigational / Q000379:methods*; D016896:Treatment Outcome; D019562:Viral Load; D028761:Withholding Treatment
chemical_list: D044966:Anti-Retroviral Agents; D004279:DNA, Viral; D012367:RNA, Viral; D001310:Auranofin; D019328:Buthionine Sulfoximine