Based on efficacy trials that have utilized viral vector-based immunogens that typically induce cell mediated immunity such as HVTN 502/STEP (9), HVTN 503/Phambili (10) and HVTN 505 (11), it remains unclear to what extent excessive CD4+ T cell activation may contribute to the increased risk of infection or explain the lack of protection observed in these studies (12). The gene discussed is CD4; the disease is infection.