Abstract
Damage to the intestinal mucosa results in the translocation of microbes from the intestinal lumen into the circulation. Microbial translocation has been proposed to trigger immune activation, inflammation, and coagulopathy, all of which are key factors that drive HIV disease progression and non-HIV comorbidities; however, direct proof of a causal link is still lacking. Here, we have demonstrated that treatment of acutely SIV-infected pigtailed macaques with the drug sevelamer, which binds microbial lipopolysaccharide in the gut, dramatically reduces immune activation and inflammation and slightly reduces viral replication. Furthermore, sevelamer administration reduced coagulation biomarkers, confirming the contribution of microbial translocation in the development of cardiovascular comorbidities in SIV-infected nonhuman primates. Together, our data suggest that early control of microbial translocation may improve the outcome of HIV infection and limit noninfectious comorbidities associated with AIDS.
Authors
Jan Kristoff, George Haret-Richter, Dongzhu Ma, Ruy M. Ribeiro, Cuiling Xu, Elaine Cornell, Jennifer L. Stock, Tianyu He, Adam D. Mobley, Samantha Ross, Anita Trichel, Cara Wilson, Russell Tracy, Alan Landay, Cristian Apetrei, Ivona Pandrea
Figure 3
Sevelamer treatment during early SIVsab infection of PTMs results in reduction of immune activation, inflammation, and viral replication.
Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)