title: Pentoxifylline, inflammation, and endothelial function in HIV-infected persons: a randomized, placebo-controlled trial.
abstract: BACKGROUND
  Untreated HIV may increase the risk of cardiovascular events. Our preliminary in vitro and in vivo research suggests that pentoxifylline (PTX) reduces vascular inflammation and improves endothelial function in HIV-infected persons not requiring antiretroviral therapy.
  
  
  METHODS
  We performed a randomized, placebo-controlled trial of PTX 400 mg orally thrice daily for 8 weeks in 26 participants. The primary endpoint was change in flow-mediated dilation (FMD) of the brachial artery after 8 weeks. Nitroglycerin-mediated dilation (NTGMD) and circulating markers of inflammation, cellular immune activation, coagulation, and metabolism were also assessed.
  
  
  RESULTS
  The difference in mean absolute change (SD) in FMD after 8 weeks between the placebo [-1.06 (1.45)%] and PTX [-1.93 (3.03)%] groups was not significant (P = 0.44). No differences in NTGMD were observed. The only significant between-group difference in the changes in biomarkers from baseline to week 8 was in soluble tumor necrosis factor receptor-1 (sTNFRI) [-83.2 pg/mL in the placebo group vs. +65.9 pg/mL in the PTX group; P = 0.03]. PTX was generally well-tolerated.
  
  
  CONCLUSIONS
  PTX did not improve endothelial function and unexpectedly increased the inflammatory biomarker sTNFRI in HIV-infected participants not requiring antiretroviral therapy. Additional interventional research is needed to reduce inflammation and cardiovascular risk in this population.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00796822.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States of America. sgupta1@iupui.edu
authors.forename: Samir K
authors.initials: SK
authors.lastname: Gupta
authors.forename: Deming
authors.initials: D
authors.lastname: Mi
authors.forename: Michael P
authors.initials: MP
authors.lastname: Dubé
authors.forename: Chandan K
authors.initials: CK
authors.lastname: Saha
authors.forename: Raymond M
authors.initials: RM
authors.lastname: Johnson
authors.forename: James H
authors.initials: JH
authors.lastname: Stein
authors.forename: Matthias A
authors.initials: MA
authors.lastname: Clauss
authors.forename: Kieren J
authors.initials: KJ
authors.lastname: Mather
authors.forename: Zeruesenay
authors.initials: Z
authors.lastname: Desta
authors.forename: Ziyue
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D015415:Biomarkers; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D008297:Male; D010431:Pentoxifylline / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D012737:Sex Factors; D016896:Treatment Outcome; D014657:Vasculitis / Q000188:drug therapy* / Q000209:etiology*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D010431:Pentoxifylline