Antibiotic and Antiinflammatory Therapy Transiently Reduces Inflammation and Hypercoagulation in Acutely SIV-Infected Pigtailed Macaques

PLoS Pathogens

Jan Kristoff¹  Benjamin B. Policicchio¹  Elaine Cornell¹  Russell Tracy¹  Jennifer L. Stock¹  George S. Haret-Richter¹  Ruy M. Ribeiro¹  Daniel N. Frank¹  Ivona Pandrea¹  Dongzhu Ma²  Tianyu He³  Anita Trichel⁴  Cristian Apetrei⁴  Cuiling Xu⁵  Cara Wilson⁶  Alan L. Landay⁷ 

[1] Center for Vaccine Research, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America;Department of Medicine, University of Colorado, Aurora, Colorado, United States of America;Department of Microbiology and Molecular Genetics, School of Medicine, University of Pittsburgh, Pittsburgh, Penssylvania, United States of America;Department of Pathology and Laboratory Medicine, University of Vermont, Burlington, Vermont, United States of America;Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, Penssylvania, United States of America;Division of Laboratory Animal Resources, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America;Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America

关键词: T cells;    Macaque;    Immune activation;    Blood plasma;    Gastrointestinal tract;    Inflammation;    SIV;    Viral replication;   

DOI  :  10.1371/journal.ppat.1005384

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Increased chronic immune activation and inflammation are hallmarks of HIV/SIV infection and are highly correlated with progression to AIDS and development of non-AIDS comorbidities, such as hypercoagulability and cardiovascular disease. Intestinal dysfunction resulting in microbial translocation has been proposed as a lead cause of systemic immune activation and hypercoagulability in HIV/SIV infection. Our goal was to assess the biological and clinical impact of a therapeutic strategy designed to reduce microbial translocation through reduction of the microbial content of the intestine (Rifaximin-RFX) and of gut inflammation (Sulfasalazine-SFZ). RFX is an intraluminal antibiotic that was successfully used in patients with hepatic encephalopathy. SFZ is an antiinflammatory drug successfully used in patients with mild to moderate inflammatory bowel disease. Both these clinical conditions are associated with increased microbial translocation, similar to HIV-infected patients. Treatment was administered for 90 days to five acutely SIV-infected pigtailed macaques (PTMs) starting at the time of infection; seven untreated SIVsab-infected PTMs were used as controls. RFX+SFZ were also administered for 90 days to three chronically SIVsab-infected PTMs. RFX+SFZ administration during acute SIVsab infection of PTMs resulted in: significantly lower microbial translocation, lower systemic immune activation, lower viral replication, better preservation of mucosal CD4+ T cells and significantly lower levels of hypercoagulation biomarkers. This effect was clear during the first 40 days of treatment and was lost during the last stages of treatment. Administration of RFX+SFZ to chronically SIVsab–infected PTMs had no discernible effect on infection. Our data thus indicate that early RFX+SFZ administration transiently improves the natural history of acute and postacute SIV infection, but has no effect during chronic infection.

【 授权许可】

CC BY