The correlates of protective immunity in HIV-1 infection include the endogenous production of compounds with anti-HIV-1 activity. These compounds can be produced independently of specific humoral or cellular immune responses. A model of compartmental inhibition of HIV-1 infection is the placenta, an organ that prevents transmission of HIV-1 to the fetus in the majority of HIV-1 pregnancies. Studies of this organ elucidated new compounds and mechanisms for prevention and treatment of HIV including the potent inhibitor of HIV-1, leukemia inhibitory factor (LIF). Besides coordinating the humoral and cellular immune responses, cytokines such as IFN-? exhibit intrinsic antiviral activity that represents the first line of defense against pathogens prior to the development of a specific immune response. The study of antiviral factors is particularly important in HIV / AIDS because of the direct destruction of the immune system by HIV-1. In this report, we focus on the identification and mechanism of endogenously produced anti-HIV factors and the overall function of these factors in the prevention and treatment of HIV / AIDS.