Instead of preventing infection, most HIV-1 vaccines in clinical trials are directed at inducing cytotoxic HIV-1-specific T cell (CTL) responses which may control viral replication and subsequently modify the clinical course of HIV-1 infection. Thus, vaccine efficacy trial designs must follow participants who become HIV-infected and monitor the course of HIV-1 infection, in order to assess the effect of vaccination on HIV-1 disease progression. This post-infection evaluation will assess time to reach specific CD4 and viral load thresholds as well as time to initiation of antiretroviral therapy. This paper discusses current literature and guidelines on the initiation of highly active antiretroviral therapy (HAART) for persons who become HIV-infected during HIV-1 vaccine trials, focusing both on acute and early HIV-1 infection, since participants in HIV-1 vaccine and other prevention trials will typically be identified within 3-6 months after HIV-1 acquisition. A standardized HAART protocol for HIV-1 vaccine efficacy trial participants who become HIV-infected is essential to the evaluation of CTL-based HIV-1 vaccines on the natural history of HIV-1 infection.