Rational Basis for an Immune Intervention in the Treatment of Primary HIV-1 Infection

During acute HIV-1 infection, a strong cellular antiviral response develops, allowing a decrease in viral replication and the establishment of a set-point in HIV-1 RNA levels within a few months. However, HIV-1 persists due to the formation of a pool of latently infected cells and immune escape mechanisms. Combination antiretroviral therapy initiated at the time of acute infection has demonstrated the capacity to block HIV-1 replication < 20 copies/mL in most cases and protect from immune depletion. Some immune responses can improve, as can responses against recall antigens and CD4 anti-HIV specific immunity, but cytotoxic T cell activity generally wanes and plasma HIV-1 RNA rebounds each time therapy is stopped. The adding of an immune intervention to antiretroviral drugs is the next step to be studied. Interleukin-2 has demonstrated its potential benefits in chronic disease and its capacity to decrease the pool of latently infected cells. Specific vaccination against HIV-1 proteins using canarypox vectors is currently being tested in combination with HAART and IL-2 during acute infection. Cytotoxic drugs, like hydroxyurea, which act by antiviral and immunologic mechanisms, could also be of interest. The next few years will tell us whether these strategies initiated early in the course of HIV-1 infection are capable of inducing viral remission.