title: Safety and immunogenicity of therapeutic DNA vaccination in individuals treated with antiretroviral therapy during acute/early HIV-1 infection.
abstract: BACKGROUND
  An effective therapeutic vaccine that could augment immune control of HIV-1 replication may abrogate or delay the need for antiretroviral therapy. AIDS Clinical Trials Group (ACTG) A5187 was a phase I/II, randomized, placebo-controlled, double-blinded trial to evaluate the safety and immunogenicity of an HIV-1 DNA vaccine (VRC-HVDNA 009-00-VP) in subjects treated with antiretroviral therapy during acute/early HIV-1 infection. (clinicaltrials.gov NCT00125099)
  
  
  METHODS
  Twenty healthy HIV-1 infected subjects who were treated with antiretroviral therapy during acute/early HIV-1 infection and had HIV-1 RNA<50 copies/mL were randomized to receive either vaccine or placebo. The objectives of this study were to evaluate the safety and immunogenicity of the vaccine. Following vaccination, subjects interrupted antiretroviral treatment, and set-point HIV-1 viral loads and CD4 T cell counts were determined 17-23 weeks after treatment discontinuation.
  
  
  RESULTS
  Twenty subjects received all scheduled vaccinations and discontinued antiretroviral therapy at week 30. No subject met a primary safety endpoint. No evidence of differences in immunogenicity were detected in subjects receiving vaccine versus placebo. There were also no significant differences in set-point HIV-1 viral loads or CD4 T cell counts following treatment discontinuation. Median set-point HIV-1 viral loads after treatment discontinuation in vaccine and placebo recipients were 3.5 and 3.7 log(10) HIV-1 RNA copies/mL, respectively.
  
  
  CONCLUSIONS
  The HIV-1 DNA vaccine (VRC-HIVDNA 009-00-VP) was safe but poorly immunogenic in subjects treated with antiretroviral therapy during acute/early HIV-1 infection. Viral set-points were similar between vaccine and placebo recipients following treatment interruption. However, median viral load set-points in both groups were lower than in historical controls, suggesting a possible role for antiretroviral therapy in persons with acute or early HIV-1 infection and supporting the safety of discontinuing treatment in this group.
  
  
  BACKGROUND
  Clinicaltrials.gov NCT00125099.
authors.affiliation: Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America. erosenberg1@mgh.harvard.edu
authors.forename: Eric S
authors.initials: ES
authors.lastname: Rosenberg
authors.forename: Barney S
authors.initials: BS
authors.lastname: Graham
authors.forename: Ellen S
authors.initials: ES
authors.lastname: Chan
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Bosch
authors.forename: Vicki
authors.initials: V
authors.lastname: Stocker
authors.forename: Janine
authors.initials: J
authors.lastname: Maenza
authors.forename: Martin
authors.initials: M
authors.lastname: Markowitz
authors.forename: Susan
authors.initials: S
authors.lastname: Little
authors.forename: Paul E
authors.initials: PE
authors.lastname: Sax
authors.forename: Ann C
authors.initials: AC
authors.lastname: Collier
authors.forename: Gary
authors.initials: G
authors.lastname: Nabel
authors.forename: Suzanne
authors.initials: S
authors.lastname: Saindon
authors.forename: Theresa
authors.initials: T
authors.lastname: Flynn
authors.forename: Daniel
authors.initials: D
authors.lastname: Kuritzkes
authors.forename: Dan H
authors.initials: DH
authors.lastname: Barouch
mesh_terms: D016915:AIDS Vaccines / Q000009:adverse effects* / Q000627:therapeutic use*; D000208:Acute Disease; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D049109:Cell Proliferation; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000276:immunology; D014611:Vaccination; D019444:Vaccines, DNA / Q000009:adverse effects* / Q000627:therapeutic use*
chemical_list: D016915:AIDS Vaccines; D012367:RNA, Viral; D019444:Vaccines, DNA; D007371:Interferon-gamma