Influence of IFNgamma co-expression on the safety and antiviral efficacy of recombinant fowlpox virus HIV therapeutic vaccines following interruption of antiretroviral therapy.
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.
Emery
S
S
National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia.
Kelleher
A D
AD
Workman
C
C
Puls
R L
RL
Bloch
M
M
Baker
D
D
Anderson
J
J
Hoy
J
J
Ip
S
S
Nalliah
K
K
Ward
L D
LD
Law
M G
MG
Cooper
D A
DA
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*
D016915:AIDS Vaccines; D019380:Anti-HIV Agents; D015683:Gene Products, gag; D015684:Gene Products, pol; D015483:HIV Antibodies; D014614:Vaccines, Synthetic; D007371:Interferon-gamma