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

Pandrea, I and Xu, C and Stock, JL and Frank, DN and Ma, D and Policicchio, BB and He, T and Kristoff, J and Cornell, E and Haret-Richter, GS and Trichel, A and Ribeiro, RM and Tracy, R and Wilson, C and Landay, AL and Apetrei, C (2016) Antibiotic and Antiinflammatory Therapy Transiently Reduces Inflammation and Hypercoagulation in Acutely SIV-Infected Pigtailed Macaques. PLoS Pathogens, 12 (1). ISSN 1553-7366

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Abstract

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.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Pandrea, I
Xu, C
Stock, JLjls329@pitt.eduJLS329
Frank, DN
Ma, Ddom13@pitt.eduDOM13
Policicchio, BBbbp6@pitt.eduBBP6
He, Ttih19@pitt.eduTIH19
Kristoff, Jjak83@pitt.eduJAK83
Cornell, E
Haret-Richter, GS
Trichel, Atrichel@pitt.eduTRICHEL0000-0002-7338-8814
Ribeiro, RM
Tracy, R
Wilson, C
Landay, AL
Apetrei, Capetreic@pitt.eduAPETREIC
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorSilvestri, GuidoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Centers: Other Centers, Institutes, or Units > Center for Vaccine Research
Date: 1 January 2016
Date Type: Publication
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Journal or Publication Title: PLoS Pathogens
Volume: 12
Number: 1
DOI or Unique Handle: 10.1371/journal.ppat.1005384
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Microbiology and Molecular Genetics
School of Medicine > Pathology
Refereed: Yes
ISSN: 1553-7366
Date Deposited: 05 Jul 2016 15:00
Last Modified: 19 Jan 2019 15:55
URI: http://d-scholarship.pitt.edu/id/eprint/28532

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