title: DNA immunization in combination with effective antiretroviral drug therapy controls viral rebound and prevents simian AIDS after treatment is discontinued.
abstract: DNA immunization in conjunction with antiretroviral therapy was evaluated in SIV-infected rhesus macaques treated with [R]-9-[2-phosphonylmethoxypropyl]adenine (PMPA). Macaques were immunized monthly with DNA vaccines expressing either SIV gag/tat or SIV gag/tat and 19 CD8+ T cell epitopes during 7 months of therapy. Half the animals from each group were additionally immunized before infection. Only 60% of the animals (4 controls, 20 vaccinated) responded to PMPA (ART responders). All 4 ART responder controls demonstrated viral rebound or CD4 decline after PMPA was withdrawn. In contrast, 17 of 20 vaccinated ART responders contained viral rebound for over 7 months after PMPA was withdrawn. Viral control correlated with stable CD4 counts, higher lymphoproliferation and an increase in the magnitude and breadth of the CD8+ T cell response. Immunizing before infection or with multi-epitopes enhanced these effects. These results demonstrate that DNA immunization during antiretroviral therapy may be an effective strategy to treat HIV infection.
authors.affiliation: PowderJect Vaccines, Inc., Middleton, WI 53562, USA. dfuller@pitt.edu
authors.forename: Deborah Heydenburg
authors.initials: DH
authors.lastname: Fuller
authors.forename: Premeela A
authors.initials: PA
authors.lastname: Rajakumar
authors.forename: Mary S
authors.initials: MS
authors.lastname: Wu
authors.forename: Christopher W
authors.initials: CW
authors.lastname: McMahon
authors.forename: Tim
authors.initials: T
authors.lastname: Shipley
authors.forename: James T
authors.initials: JT
authors.lastname: Fuller
authors.forename: Afrouz
authors.initials: A
authors.lastname: Bazmi
authors.forename: Anita M
authors.initials: AM
authors.lastname: Trichel
authors.forename: Todd M
authors.initials: TM
authors.lastname: Allen
authors.forename: Bianca
authors.initials: B
authors.lastname: Mothe
authors.forename: Joel R
authors.initials: JR
authors.lastname: Haynes
authors.forename: David I
authors.initials: DI
authors.lastname: Watkins
authors.forename: Michael
authors.initials: M
authors.lastname: Murphey-Corb
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D018450:Disease Progression; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology; D015696:Gene Products, tat / Q000235:genetics / Q000276:immunology; D016233:Immunotherapy, Active / Q000379:methods; D008253:Macaca mulatta; D063065:Organophosphonates / Q000008:administration & dosage* / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000187:drug effects / Q000276:immunology*; D013223:Statistics as Topic; D000068698:Tenofovir; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology; D014766:Viremia / Q000517:prevention & control*; D028761:Withholding Treatment
chemical_list: D019380:Anti-HIV Agents; D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D015696:Gene Products, tat; D063065:Organophosphonates; D012367:RNA, Viral; D019444:Vaccines, DNA; D000068698:Tenofovir; D000225:Adenine