title: Amplified antigen-specific immune responses in HIV-1 infected individuals in a double blind DNA immunization and therapy interruption trial.
abstract: Immunotherapy in patients with HIV-1 infection aims to restore and broaden immunological competence, reduce viral load and thereby permit longer periods without combined antiretroviral treatment (cART). Twelve HIV-1-infected patients on cART were immunized on the skin with DNA plasmids containing genes of several HIV-1 subtypes with or without the addition of hydroxyurea (HU), or with placebo. The mean net gain of HIV-specific CD8+ T cell responses were higher and broader in the HIV DNA vaccine groups compared to non-vaccinated individuals (p<0.05). The vaccine-induced immune responses per se had no direct effect on viral replication. In all patients combined, including placebo, the viral set point after a final structured therapy interruption (STI) was lower than prior to initiation of cART (p=0.003). Nadir CD4 levels appeared to strongly influence the post-STI viral titers. After the sixth immunization or placebo, patients could stay off cART for a median time of 15 months. The study shows that HIV DNA immunization induces broader and higher magnitudes of HIV-specific immune responses compared to structured therapy interruptions alone. Although compromised by small numbers of patients, the study also demonstrates that well-monitored STI may safely function as an immunological read out of HIV vaccine efficacy.
authors.affiliation: Karolinska Institutet and Swedish Institute for Infectious Disease Control, Nobels väg 18, 171 82 Stockholm, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Gudmundsdotter
authors.forename: B
authors.initials: B
authors.lastname: Wahren
authors.forename: B K
authors.initials: BK
authors.lastname: Haller
authors.forename: A
authors.initials: A
authors.lastname: Boberg
authors.forename: U
authors.initials: U
authors.lastname: Edbäck
authors.forename: D
authors.initials: D
authors.lastname: Bernasconi
authors.forename: S
authors.initials: S
authors.lastname: Buttò
authors.forename: H
authors.initials: H
authors.lastname: Gaines
authors.forename: N
authors.initials: N
authors.lastname: Imami
authors.forename: F
authors.initials: F
authors.lastname: Gotch
authors.forename: F
authors.initials: F
authors.lastname: Lori
authors.forename: J
authors.initials: J
authors.lastname: Lisziewicz
authors.forename: E
authors.initials: E
authors.lastname: Sandström
authors.forename: B
authors.initials: B
authors.lastname: Hejdeman
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000276:immunology; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004311:Double-Blind Method; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control* / Q000628:therapy*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008004:Licensure; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D010957:Plasmids / Q000008:administration & dosage; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology; D019562:Viral Load
chemical_list: D016915:AIDS Vaccines; D019380:Anti-HIV Agents; D000956:Antigens, Viral; D010919:Placebos; D019444:Vaccines, DNA