Differential effects of HIV-1 protease inhibitors on dendritic cell immunophenotype and function

Recent findings show that human immunodeficiency virus (HIV)-1 protease inhibitors designed to specifically inhibit the aspartic protease of HIV-1 nonetheless exert various effects on immune cell function in vitro and in vivo. Dendritic cells (DC), central players of the immune system, express several aspartic proteases that are important for DC function. In the present study, we demonstrate that all of the HIV-1 protease inhibitors tested affect DC maturation. In addition, saquinavir had a strong inhibitory effect on the T-cell stimulatory capacity of mature DC. In contrast, indinavir had only a slight effect on DC induced T-cell proliferation and allowed efficient transduction of DC with a replication-incompetent HIV-1 vector designed for DC-based immunotherapy. HIV-1 protease inhibitors that have little or no effect on DC function may be preferable for combination with immunotherapy for HIV/AIDS.