Background: Immunisation by priming with plasmid DNA encoding HIV-1 genes followed by a recombinant vector boost is a potent method of inducing HIV-1-specific CTL responses. Viral suppression after the initiation of HAART is often associated with a decline in CTL frequencies. Therapeutic vaccination using a prime-boost strategy in HAART-treated patients (pts)may lead to enhancement or recovery of HIV-1-specific CTL. We are investigating the safety, tolerability, and immunogenicity of a candidate HIV DNA gag/multi-epitope vaccine, pTHr.HIVA, in HIV-1 seropositive subjects receiving HAART.

Methods: Immunisation with 2 x 500 mg doses of DNA administered by intramuscular injection 3 wks apart in 10 HAART-treated subjects with undetectable plasma virus load and CD4 count > 300 cells/ml.

Results: Six (6) subjects have been enrolled to date. Five (5) have received at least 1 DNA immunisation, with no side effects. Plasma virus load has remained undetectable in all vaccinees and there have been no significant changes in CD4 count. Pre-immunisation CD8⁺ T-cell responses to at least 1/7 peptide pools based on the vaccine sequence were detected by the IFN-g Elispot assay in 5/6 subjects and are being quantified at days 14, 21, 35, 49, 77, and 105. In 1 subject there was a modest increase in CD8⁺ T-cells specific for 1 of the gag peptide pools by day 35. Baseline HIV-specific CD4⁺ T-cells were not detected in any subject by elispot or flow cytometric analysis of intracellular IFN-g. Follow-up is ongoing.

Conclusions: Preliminary data suggest that immunisation with pTHr.HIVA is safe and well-tolerated by HIV-1 seropositive subjects. Prime-boost immunizations using DNA followed by recombinant modified vaccinia virus Ankara vaccines are planned.