The gut microbiota in HIV infection: dysbiosis, immune dysfunction, and implications for disease progression and management

HIV infection is characterized by the loss of CD4+ T lymphocytes, particularly within gut-associated lymphoid tissue, a process that begins in the early stages and persists throughout disease progression. The inflammatory state of the intestinal wall or the products derived from cell damage contribute to alterations in intestinal microbial composition. People with human immunodeficiency virus (PWH) exhibit reduced microbial diversity and richness, with notable depletion of families such as Lachnospiraceae, Ruminococcaceae, and Rikenellaceae, alongside a compensatory increase in other butyrate-producing taxa. A reduction in Akkermansia, a genus involved in mucus layer maintenance, is also observed. These microbial shifts are influenced by factors including immune status, sexual practices, diet and antiretroviral therapy. Disruption of the intestinal barrier, potentially compounded by microbial imbalance, promotes translocation of bacteria and microbial products, leading to sustained activation of both innate and adaptive immune responses. Current evidence suggests a predominantly associative link between this chronic immune activation, possibly mediated through endothelial dysfunction, platelet activation, and coagulation and fibrinolysis pathways, and the increased prevalence of atherosclerosis observed in PWH. Future research should focus on translating these associative findings into personalized therapeutic strategies, such as targeted microbiota modulation, to mitigate inflammation and reduce cardiovascular risk.