Therapeutic immunization of HIV-1-infected individuals may induce and/or enhance HIV-1-specific immune responses and decrease the dependency on antiretroviral drug treatment. However, repeated immunizations with live-recombinant vectors may induce vector-specific immune responses that interfere with the elicitation of vigorous immune responses to the desired antigen. Therefore, the use of mixed-modality vaccinations may be necessary to induce sustained virus-specific immune responses in HIV-1-infected individuals treated with antiretroviral therapy (ART). Thus, the relative immunogenicity of various vaccine modalities needs to be assessed. Here we compared the immunogenicity of two vaccine candidates, the canarypox-based ALVAC-SIV-gag-pol-env (ALVAC-SIV-gpe) and the vaccinia-based NYVAC-SIV-gag-pol-env (NYVAC-SIV-gpe), in rhesus macaques infected with SIVmac251 and treated with ART by 2 weeks postinfection. Both ALVAC-SIV-gpe and NYVAC-SIV-gpe vaccine candidates induced and/or enhanced a virus-specific CD8+ T cell response to a similar extent, as demonstrated by tetramer staining of Gag-specific CD8+ T cells. Similarly, both vaccines elicited comparable lymphoproliferative responses (LPRs) to the SIV p27 Gag and gp120 Env proteins. Thus, both these vaccine modalities alone or in combination may be suitable candidate vaccines for immune therapy of HIV-1-infected individuals. © 2002 Elsevier Science (USA).