The early immune response to HIV-1 infection is crucial for determining the clinical course of the disease. Recent studies have revealed that the HIV-1 quasispecies arising from mucosal infection typically derive from a single transmitted virus, and the first effective immune responses drive the selection of virus escape mutations. Strong innate and adaptive immune responses occur but are too late to eliminate the infection. This review discusses recent advances in understanding the kinetics and quality of early immune responses to HIV-1, including the nature of the transmitted virus, the role of genetically influenced immune responses, and the rate of virus mutation. It also reviews the nature of innate and adaptive immune responses during the early phase of infection, drawing from studies of humans and macaques infected with HIV-1 and SIV, respectively. The review highlights the importance of these early events in shaping the viral set point and the potential for developing a successful preventive HIV-1 vaccine. The findings suggest that a vaccine should aim to prime early and broad immune responses, particularly CD8+ T cell responses to multiple epitopes, to control viral replication and prevent extensive CD4+ T cell depletion.The early immune response to HIV-1 infection is crucial for determining the clinical course of the disease. Recent studies have revealed that the HIV-1 quasispecies arising from mucosal infection typically derive from a single transmitted virus, and the first effective immune responses drive the selection of virus escape mutations. Strong innate and adaptive immune responses occur but are too late to eliminate the infection. This review discusses recent advances in understanding the kinetics and quality of early immune responses to HIV-1, including the nature of the transmitted virus, the role of genetically influenced immune responses, and the rate of virus mutation. It also reviews the nature of innate and adaptive immune responses during the early phase of infection, drawing from studies of humans and macaques infected with HIV-1 and SIV, respectively. The review highlights the importance of these early events in shaping the viral set point and the potential for developing a successful preventive HIV-1 vaccine. The findings suggest that a vaccine should aim to prime early and broad immune responses, particularly CD8+ T cell responses to multiple epitopes, to control viral replication and prevent extensive CD4+ T cell depletion.