title: Indicators of therapeutic effect in FIT-06, a Phase II trial of a DNA vaccine, GTU(®)-Multi-HIVB, in untreated HIV-1 infected subjects.
abstract: BACKGROUND
  Combination highly active antiretroviral therapy (HAART) has significantly decreased HIV-1 related morbidity and mortality globally transforming HIV into a controllable condition. HAART has a number of limitations though, including limited access in resource constrained countries, which have driven the search for simpler, affordable HIV-1 treatment modalities. Therapeutic HIV-1 vaccines aim to provide immunological support to slow disease progression and decrease transmission. We evaluated the safety, immunogenicity and clinical effect of a novel recombinant plasmid DNA therapeutic HIV-1 vaccine, GTU(®)-multi-HIVB, containing 6 different genes derived from an HIV-1 subtype B isolate.
  
  
  METHODS
  63 untreated, healthy, HIV-1 infected, adults between 18 and 40 years were enrolled in a single-blinded, placebo-controlled Phase II trial in South Africa. Subjects were HIV-1 subtype C infected, had never received antiretrovirals, with CD4 ≥ 350 cells/mm(3) and pHIV-RNA ≥ 50 copies/mL at screening. Subjects were allocated to vaccine or placebo groups in a 2:1 ratio either administered intradermally (ID) (0.5mg/dose) or intramuscularly (IM) (1mg/dose) at 0, 4 and 12 weeks boosted at 76 and 80 weeks with 1mg/dose (ID) and 2mg/dose (IM), respectively. Safety was assessed by adverse event monitoring and immunogenicity by HIV-1-specific CD4+ and CD8+ T-cells using intracellular cytokine staining (ICS), pHIV-RNA and CD4 counts.
  
  
  RESULTS
  Vaccine was safe and well tolerated with no vaccine related serious adverse events. Significant declines in log pHIV-RNA (p=0.012) and increases in CD4+ T cell counts (p=0.066) were observed in the vaccine group compared to placebo, more pronounced after IM administration and in some HLA haplotypes (B*5703) maintained for 17 months after the final immunisation.
  
  
  CONCLUSIONS
  The GTU(®)-multi-HIVB plasmid recombinant DNA therapeutic HIV-1 vaccine is safe, well tolerated and favourably affects pHIV-RNA and CD4 counts in untreated HIV-1 infected individuals after IM administration in subjects with HLA B*57, B*8101 and B*5801 haplotypes.
authors.affiliation: Lancet Laboratories, Richmond, Johannesburg, South Africa. eftyxia.vardas@lancet.co.za
authors.forename: Eftyhia
authors.initials: E
authors.lastname: Vardas
authors.forename: Ioana
authors.initials: I
authors.lastname: Stanescu
authors.forename: Mika
authors.initials: M
authors.lastname: Leinonen
authors.forename: Kim
authors.initials: K
authors.lastname: Ellefsen
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pantaleo
authors.forename: Minna
authors.initials: M
authors.lastname: Valtavaara
authors.forename: Mart
authors.initials: M
authors.lastname: Ustav
authors.forename: Kalevi
authors.initials: K
authors.lastname: Reijonen
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D000163:Acquired Immunodeficiency Syndrome / Q000628:therapy* / Q000821:virology; D000328:Adult; D018791:CD4 Lymphocyte Count; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D005260:Female; D005838:Genotype; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007271:Injections, Intradermal; D007273:Injections, Intramuscular; D008297:Male; D010919:Placebos / Q000008:administration & dosage; D010957:Plasmids / Q000008:administration & dosage; D012367:RNA, Viral / Q000097:blood; D013019:South Africa; D016896:Treatment Outcome; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D019562:Viral Load; D055815:Young Adult
chemical_list: D016915:AIDS Vaccines; D010919:Placebos; D012367:RNA, Viral; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic