title: Influence of IFNgamma co-expression on the safety and antiviral efficacy of recombinant fowlpox virus HIV therapeutic vaccines following interruption of antiretroviral therapy.
abstract: Therapeutic immunization to stimulate host immune responses and control human immunodeficiency virus (HIV-1) replication is being investigated as a supplementary treatment for the management of HIV infection. On completion of an earlier study involving three vaccinations while taking combination antiretroviral therapy (CART), twenty-five subjects with plasma viral load (pVL) <50 copies/mL received a booster vaccination with either placebo (n = 7); fowl pox vaccine (rFPV) expressing HIV-1 Gag/Pol; [partial construct- PC (n = 8)] or rFPV coexpressing HIV-1 Gag/Pol and human interferon gamma[full construct - FC (n = 10)]. One week after the booster vaccination, participants stopped ART and were monitored for safety, pVL and immunological parameters for < or =20 weeks. The time weighted mean change (SD) from baseline plasma HIV RNA was 1.80 (0.72), 1.78 (0.91) and 0.96 (0.91) log(10) copies/mL for placebo, PC and FC recipients respectively (p = 0.06; mean differences between placebo and FC). Laboratory evaluations did not reveal differences in anti-HIV specific immune responses between study arms. No difference between treatment arms for host genetic factors known to affect pVL was demonstrated. In conclusion, vaccination with FC was associated with a trend toward lower rates of HIV replication following cessation of ART relative to placebo or PC. The promising antiretrovirological effect supports further study of FC in a larger trial with a broader population of patients with HIV disease.
authors.affiliation: National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Emery
authors.forename: A D
authors.initials: AD
authors.lastname: Kelleher
authors.forename: C
authors.initials: C
authors.lastname: Workman
authors.forename: R L
authors.initials: RL
authors.lastname: Puls
authors.forename: M
authors.initials: M
authors.lastname: Bloch
authors.forename: D
authors.initials: D
authors.lastname: Baker
authors.forename: J
authors.initials: J
authors.lastname: Anderson
authors.forename: J
authors.initials: J
authors.lastname: Hoy
authors.forename: S
authors.initials: S
authors.lastname: Ip
authors.forename: K
authors.initials: K
authors.lastname: Nalliah
authors.forename: L D
authors.initials: LD
authors.lastname: Ward
authors.forename: M G
authors.initials: MG
authors.lastname: Law
authors.forename: D A
authors.initials: DA
authors.lastname: Cooper
mesh_terms: D016915:AIDS Vaccines / Q000009:adverse effects* / Q000235:genetics / Q000276:immunology*; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D005587:Fowlpox virus / Q000235:genetics*; D015683:Gene Products, gag / Q000276:immunology; D015684:Gene Products, pol / Q000276:immunology; D005822:Genetic Vectors; D015483:HIV Antibodies; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000008:administration & dosage / Q000276:immunology*; D016032:Randomized Controlled Trials as Topic; D012449:Safety; D014614:Vaccines, Synthetic / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D019380:Anti-HIV Agents; D015683:Gene Products, gag; D015684:Gene Products, pol; D015483:HIV Antibodies; D014614:Vaccines, Synthetic; D007371:Interferon-gamma