title: Therapeutic Vaccination With Dendritic Cells Loaded With Autologous HIV Type 1-Infected Apoptotic Cells.
abstract: BACKGROUND
  We report the results of a phase I/II, open-label, single-arm clinical trial to evaluate the safety and anti-human immunodeficiency virus type 1 (HIV-1) efficacy of an autologous dendritic cell (DC)-based HIV-1 vaccine loaded with autologous HIV-1-infected apoptotic cells.
  
  
  METHODS
  Antiretroviral therapy (ART)-naive individuals were enrolled, and viremia was suppressed by ART prior to delivery of 4 doses of DC-based vaccine. Participants underwent treatment interruption 6 weeks after the third vaccine dose. The plasma HIV-1 RNA level 12 weeks after treatment interruption was compared to the pre-ART (ie, baseline) level.
  
  
  RESULTS
  The vaccine was safe and well tolerated but did not prevent viral rebound during treatment interruption. Vaccination resulted in a modest but significant decrease in plasma viremia from the baseline level (from 4.53 log10 copies/mL to 4.27 log10 copies/mL;P= .05). Four of 10 participants had a >0.70 log10 increase in the HIV-1 RNA load in plasma following vaccination, despite continuous ART. Single-molecule sequencing of HIV-1 RNA in plasma before and after vaccination revealed increases in G>A hypermutants in gag and pol after vaccination, which suggests cytolysis of infected cells.
  
  
  CONCLUSIONS
  A therapeutic HIV-1 vaccine based on DCs loaded with apoptotic bodies was safe and induced T-cell activation and cytolysis, including HIV-1-infected cells, in a subset of study participants.
  
  
  BACKGROUND
  NCT00510497.
authors.affiliation: Division of Infectious Diseases, University of Pittsburgh School of Medicine.
authors.forename: Bernard J C
authors.initials: BJ
authors.lastname: Macatangay
authors.affiliation: Division of Infectious Diseases, University of Pittsburgh School of Medicine.
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Riddler
authors.affiliation: Division of Infectious Diseases, University of Pittsburgh School of Medicine.
authors.forename: Nicole D
authors.initials: ND
authors.lastname: Wheeler
authors.affiliation: National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Spindler
authors.affiliation: Division of Infectious Diseases, University of Pittsburgh School of Medicine.
authors.forename: Mariam
authors.initials: M
authors.lastname: Lawani
authors.affiliation: Division of Infectious Diseases, University of Pittsburgh School of Medicine.
authors.forename: Feiyu
authors.initials: F
authors.lastname: Hong
authors.affiliation: Hillman Cancer Center, University of Pittsburgh Medical Center.
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Buffo
authors.affiliation: Hillman Cancer Center, University of Pittsburgh Medical Center.
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Whiteside
authors.affiliation: National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Mary F
authors.initials: MF
authors.lastname: Kearney
authors.affiliation: Division of Infectious Diseases, University of Pittsburgh School of Medicine.
authors.forename: John W
authors.initials: JW
authors.lastname: Mellors
authors.affiliation: Department of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, Pennsylvania.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Rinaldo
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000328:Adult; D017209:Apoptosis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation / Q000821:virology; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D014182:Transplantation, Autologous; D019562:Viral Load / Q000276:immunology
chemical_list: D016915:AIDS Vaccines
keywords: HIV-1; apoptotic cell; dendritic cell; residual viremia; therapeutic vaccine