1) A healthy gut is characterized by homeostasis between the immune system and the microbiome. 2) Though the impact of the baseline microbiota on HIV infection is unknown, it is possible that gut microbes could impact (A) transmission, potentially by activating CD4+ T cells. (B) HIV infection leads to CD4+ T cell death and immune depletion, and loss of immune regulation of gut bacteria, resulting in a dysbiotic microbiome. (C) Translocation of dysbiotic bacteria leads to (D) immune activation and further HIV infection of activated CD4+ T cells. 3) ART suppresses viral replication but does not fully restore gut immunity; dysbiosis is sustained during ART and microbial translocation continues to cause chronic immune activation. 4) A healthy gut may be restored by supplementing ART with pro/prebiotics or diets that encourage growth of beneficial bacteria, and with immunotherapy that could help reconstitute gut immunity and restore immune regulation of the microbiome.