Early microbial translocation blockade reduces SIV-mediated inflammation and viral replication.
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.
Jan
J
Kristoff
George
G
Haret-Richter
Dongzhu
D
Ma
Ruy M
RM
Ribeiro
Cuiling
C
Xu
Elaine
E
Cornell
Jennifer L
JL
Stock
Tianyu
T
He
Adam D
AD
Mobley
Samantha
S
Ross
Anita
A
Trichel
Cara
C
Wilson
Russell
R
Tracy
Alan
A
Landay
Cristian
C
Apetrei
Ivona
I
Pandrea
D000818:Animals; D018988:Bacterial Translocation / Q000187:drug effects*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D015658:HIV Infections / Q000382:microbiology / Q000628:therapy; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology / Q000821:virology; D008254:Macaca nemestrina; D011073:Polyamines / Q000494:pharmacology*; D000069603:Sevelamer; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000382:microbiology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000502:physiology; D019562:Viral Load / Q000187:drug effects; D014779:Virus Replication
D011073:Polyamines; D000069603:Sevelamer