While these results rule out the use of this single-cycle vector design as an attenuation strategy for HCMV-based HIV vaccines, this strategy could still be useful in situations where lasting conventional, effector-differentiated MHC-Ia–restricted CD8+ T cells are required and sufficient for protection against infectious diseases or cancer, potentially including CMV itself, particularly for HCMV-negative or immunocompromised vaccine recipients. This evidence concerns the gene CD8A and infectious disease.