Complex recombinant fowlpoxvirus (rFPV) vaccines expressing both HIV-1 antigens and type 1 cytokines could facilitate the induction of cellular immunity against HIV-1. A single rFPV expressing both HIV-1gag/pol and human interferon-gamma (FPVgag/pol-IFNgamma) was constructed and assessed as a therapeutic vaccine for safety and immunogenicity in macaques (Macaca nemestrina) previously infected with HIV-1. FPV gag/pol-IFNgamma vaccinations were safe and enhanced T cell proliferative responses to Gag antigens (but not control tetanus antigens). Enhanced CTL responses to gag/pol antigens were also observed following IFNgamma expressing vaccinations. Since cellular immunity may be critical to controlling or preventing HIV-1 infection, these observations suggest that avipox vectors co-expressing IFNgamma should be further evaluated as therapeutic or preventive HIV-1 vaccines.