title: Intradermal injection of a Tat Oyi-based therapeutic HIV vaccine reduces of 1.5 log copies/mL the HIV RNA rebound median and no HIV DNA rebound following cART interruption in a phase I/II randomized controlled clinical trial.
abstract: BACKGROUND
  A Tat Oyi vaccine preparation was administered with informed consent to 48 long-term HIV-1 infected volunteers whose viral loads had been suppressed by antiretroviral therapy (cART). These volunteers were randomized in double-blind method into four groups (n = 12) that were injected intradermally with 0, 11, 33, or 99 µg of synthetic Tat Oyi proteins in buffer without adjuvant at times designated by month 0 (M0), M1 and M2, respectively. The volunteers then underwent a structured treatment interruption between M5 and M7.
  
  
  RESULTS
  The primary outcomes of this phase I/IIa clinical trial were the safety and lowering the extent of HIV RNA rebound after cART interruption. Only one undesirable event possibly due to vaccination was observed. The 33 µg dose was most effective at lowering the extent of HIV RNA and DNA rebound (Mann and Whitney test, p = 0.07 and p = 0.001). Immune responses against Tat were increased at M5 and this correlated with a low HIV RNA rebound at M6 (p = 0.01).
  
  
  CONCLUSIONS
  This study suggests in vivo that extracellular Tat activates and protects HIV infected cells. The Tat Oyi vaccine in association with cART may provide an efficient means of controlling the HIV-infected cell reservoir.
authors.affiliation: ETRAV Laboratory, Faculty of Pharmacy, Centre National de la Recherche Scientifique (CNRS), Aix Marseille University, 27 Boulevard Jean Moulin, 13385, Marseille, France. erwann.loret@univ-amu.fr.
authors.forename: Erwann P
authors.initials: EP
authors.lastname: Loret
authors.affiliation: ETRAV Laboratory, Faculty of Pharmacy, Centre National de la Recherche Scientifique (CNRS), Aix Marseille University, 27 Boulevard Jean Moulin, 13385, Marseille, France.|Pharmacie Usage Interne, AP-HM, UHC «la Conception», 147 Bd Baille, 13385, Marseille, France.
authors.forename: Albert
authors.initials: A
authors.lastname: Darque
authors.affiliation: Centre de Pharmacologie Clinique et Evaluations Thérapeutiques (AP-HM), UHC «la Timone», 28 Boulevard Jean Moulin, 13385, Marseille, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Jouve
authors.affiliation: ETRAV Laboratory, Faculty of Pharmacy, Centre National de la Recherche Scientifique (CNRS), Aix Marseille University, 27 Boulevard Jean Moulin, 13385, Marseille, France.
authors.forename: Elvenn A
authors.initials: EA
authors.lastname: Loret
authors.affiliation: ETRAV Laboratory, Faculty of Pharmacy, Centre National de la Recherche Scientifique (CNRS), Aix Marseille University, 27 Boulevard Jean Moulin, 13385, Marseille, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Nicolino-Brunet
authors.affiliation: Centre d'Investigation Clinique, Assistance Publique -Hôpitaux de Marseille (AP-HM), University Hospital Center (UHC) «la Conception», 147 Bd Baille, 13385, Marseille, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Morange
authors.affiliation: Centre d'Investigation Clinique, Assistance Publique -Hôpitaux de Marseille (AP-HM), University Hospital Center (UHC) «la Conception», 147 Bd Baille, 13385, Marseille, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Castanier
authors.affiliation: Centre d'Investigation Clinique, Assistance Publique -Hôpitaux de Marseille (AP-HM), University Hospital Center (UHC) «la Conception», 147 Bd Baille, 13385, Marseille, France.
authors.forename: Josiane
authors.initials: J
authors.lastname: Casanova
authors.affiliation: Centre d'Investigation Clinique, Assistance Publique -Hôpitaux de Marseille (AP-HM), University Hospital Center (UHC) «la Conception», 147 Bd Baille, 13385, Marseille, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Caloustian
authors.affiliation: Pharmacie Usage Interne, AP-HM, UHC «la Conception», 147 Bd Baille, 13385, Marseille, France.
authors.forename: Charléric
authors.initials: C
authors.lastname: Bornet
authors.affiliation: Pharmacie Usage Interne, AP-HM, UHC «la Conception», 147 Bd Baille, 13385, Marseille, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Coussirou
authors.affiliation: Pharmacie Usage Interne, AP-HM, UHC «la Conception», 147 Bd Baille, 13385, Marseille, France.
authors.forename: Jihen
authors.initials: J
authors.lastname: Boussetta
authors.affiliation: Unité Mixte de Recherche CNRS 5251, Institut de Mathématique de Bordeaux, CNRS, Bordeaux 2 University, 33000, Bordeaux, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Couallier
authors.affiliation: Centre de Pharmacologie Clinique et Evaluations Thérapeutiques (AP-HM), UHC «la Timone», 28 Boulevard Jean Moulin, 13385, Marseille, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Blin
authors.affiliation: Centre d'Investigation Clinique, Assistance Publique -Hôpitaux de Marseille (AP-HM), University Hospital Center (UHC) «la Conception», 147 Bd Baille, 13385, Marseille, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Dussol
authors.affiliation: ETRAV Laboratory, Faculty of Pharmacy, Centre National de la Recherche Scientifique (CNRS), Aix Marseille University, 27 Boulevard Jean Moulin, 13385, Marseille, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Ravaux
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000628:therapy*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007271:Injections, Intradermal; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D016896:Treatment Outcome; D019562:Viral Load; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D044966:Anti-Retroviral Agents; D004279:DNA, Viral; D012367:RNA, Viral; D054322:tat Gene Products, Human Immunodeficiency Virus
keywords: ART interruption; Clinical trial; HIV; Tat; Vaccine