Targeting the Gut Microbiome in HIV/AIDS: New Therapeutic Opportunities

SUMMARY Despite major advances in HIV antiretroviral therapy (ART), complete elimination of the disease has not been achieved. Recently, the importance of the gutassociated lymphoid tissues (GALT) and the resident microbiota in HIV pathogenesis has been highlighted. The GALT is the largest of the human lymphoid organs and is home to the highest number of CD4+ T cells in the body. Chronic HIV infection is associated with significant metabolic pathology, including changes to the microbial composition of the gut. However, the exact mechanism by which the microbiome contributes to HIV disease progression is still unclear. It is possible that an inflammatory cycle in which changes to the gut microbiota leads to impairment of the gut mucosal barrier function, resulting in leakage of bacterial members of the gut into systemic circulation. This article will explore the current understanding of how HIV changes the gut microbiota and what mechanisms may link these changes to immune cell loss and disease progression. Chronic immune activation is a key component of HIV-pathogenesis and may underscore the depletion of CD4+ T cells. Understanding this link highlights the possible role of a master regulator within the gut mucosa, thus uncovering a potential therapeutic target that may slow HIV progression.