The recent advances in the understanding of primary HIV-1 infection and the development of well-tolerated antiretroviral therapies have highlighted the potential impact of early treatment initiation on immune responses and gut mucosal barrier dysfunction. Immunological and virological assessments in the blood as well as in gut-associated lymphoid tissues during the early phase of infection indicate the crucial role of HIV-1-specific responses and non-specific immune activation in disease progression. The clinical benefit of early antiretroviral therapy has been somewhat disappointing, with the exception of a small group of patients exhibiting sustained control of HIV replication after transient antiretroviral therapy, designated as post-treatment controllers. This review focuses on the influences of antiretroviral therapy initiated early or very early in the course of infection on the clinical and immunological outcomes as well as its impact on the gut mucosal dysfunction. The evidence presented herein paves the way for the development of immunological interventions combined with early antiretroviral therapy to enhance HIV-1-specific responses and to modulate immune activation that will contribute to HIV remission and cure.