title: Safety, tolerability, and immunogenicity of repeated doses of dermavir, a candidate therapeutic HIV vaccine, in HIV-infected patients receiving combination antiretroviral therapy: results of the ACTG 5176 trial.
abstract: BACKGROUND
  HIV-specific cellular immune responses are associated with control of viremia and delayed disease progression. An effective therapeutic vaccine could mimic these effects and reduce the need for continued antiretroviral therapy. DermaVir, a topically administered plasmid DNA-nanomedicine expressing HIV (CladeB) virus-like particles consisting of 15 antigens, induces predominantly central memory T-cell responses.
  
  
  METHODS
  Treated HIV-infected adults (HIV RNA <50 and CD4 >350) were randomized to placebo or escalating DermaVir doses (0.1 or 0.4 mg of plasmid DNA at weeks 1, 7, and 13 in the low- and intermediate-dose groups and 0.8 mg at weeks 0, 1, 6, 7, 12, and 13 in the high-dose group), n = 5-6 evaluable subjects per group. Immunogenicity was assessed by a 12-day cultured interferon-γ enzyme-linked immunosorbent spot assay at baseline and at weeks 9, 17, and 37 using 1 Tat/Rev and 3 overlapping Gag peptide pools (p17, p24, and p15).
  
  
  RESULTS
  Groups were comparable at baseline. The study intervention was well tolerated, without dose-limiting toxicities. Most responses were highest at week 17 (4 weeks after last vaccination) when Gag p24 responses were significantly greater among intermediate-dose group compared with control subjects [median (IQR): 67,600 (5633-74,368) versus 1194 (9-1667)] net spot-forming units per million cells, P = 0.032. In the intermediate-dose group, there was also a marginal Gag p15 response increase from baseline to week 17 [2859 (1867-56,933), P = 0.06], and this change was significantly greater than in the placebo group [0 (-713 to 297), P = 0.016].
  
  
  CONCLUSIONS
  DermaVir administration was associated with a trend toward greater HIV-specific, predominantly central memory T-cell responses. The intermediate DermaVir dose tended to show the greatest immunogenicity, consistent with previous studies in different HIV-infected patient populations.
authors.affiliation: *Division of Infectious Diseases and Center for AIDS Research, Case Western Reserve University/University Hospitals of Cleveland, Cleveland, OH; †Division of Infectious Diseases, University of California Davis Medical Center, Sacramento, CA; ‡Statistical and Data Analysis Center, Harvard School of Public Health, Boston, MA; §Division of Infectious Diseases and HIV Medicine, Drexel University College of Medicine, Philadelphia, PA; ‖University of Pittsburgh, Pittsburgh, PA; ¶Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, MD; #Department of Medicine, Rush University Medical Center, Chicago, IL; **ViroStatics srl, Sassari, Italy; ††Genetic Immunity, Budapest, Hungary; ‡‡Genetic Immunity, McLean, VA; and §§Social & Scientific Systems, Inc, Silver Spring, MD.
authors.forename: Benigno
authors.initials: B
authors.lastname: Rodriguez
authors.forename: David M
authors.initials: DM
authors.lastname: Asmuth
authors.forename: Roy M
authors.initials: RM
authors.lastname: Matining
authors.forename: John
authors.initials: J
authors.lastname: Spritzler
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Jacobson
authors.forename: Robbie B
authors.initials: RB
authors.lastname: Mailliard
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Li
authors.forename: Ana I
authors.initials: AI
authors.lastname: Martinez
authors.forename: Allan R
authors.initials: AR
authors.lastname: Tenorio
authors.forename: Franco
authors.initials: F
authors.lastname: Lori
authors.forename: Julianna
authors.initials: J
authors.lastname: Lisziewicz
authors.forename: Suria
authors.initials: S
authors.lastname: Yesmin
authors.forename: Charles R
authors.initials: CR
authors.lastname: Rinaldo
authors.forename: Richard B
authors.initials: RB
authors.lastname: Pollard
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes; D004359:Drug Therapy, Combination; D006801:Humans; D007115:Immunization Schedule; D012367:RNA, Viral; D019562:Viral Load; D014766:Viremia
chemical_list: D016915:AIDS Vaccines; D019380:Anti-HIV Agents; C501366:DermaVir; D012367:RNA, Viral