title: Changes in thrombolytic and inflammatory markers after initiation of indinavir- or amprenavir-based antiretroviral therapy.
abstract: HIV-infected subjects who have lipodystrophy and insulin resistance on prolonged antiretroviral therapy have elevated levels of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) antigens, markers of impaired thrombolysis that are associated with hyperinsulinemia and increased cardiovascular risk. We studied HIV-infected, protease inhibitor (PI)-naive adults treated with indinavir (n = 11) or amprenavir (n = 14) plus two nucleoside reverse transcriptase inhibitors enrolled in two independent prospective trials. Antiretroviral and immune responses were similar in both studies. Over 8 wk, indinavir was associated with decreased insulin sensitivity, whereas amprenavir was not. Levels of tPA antigen declined by approx 25% with both treatments (p < 0.05 for each); levels of PAI-1 antigen did not change. Levels of the inflammatory marker soluble tumor necrosis factor-alpha receptor II (sTNFr2) correlated positively with tPA antigen (r = 0.33, p = 0.02), and mean (SD) plasma concentrations of sTNFr also declined with treatment (4.44 +/- 1.11 ng/mL pretherapy, 3.75 +/- 1.21 posttherapy, p = 0.007). Short-term improvement in a marker of impaired thrombolysis and increased vascular risk can occur during PI-based antiretroviral therapy, perhaps as a consequence of improvement in HIV-related inflammation. This improvement occurred independent of development of insulin resistance, which occurred only with indinavir.
authors.affiliation: Department of Medicine and Division of Infectious Diseases, Indiana University School of Medicine, Indianapolis, IN 46202-2879, USA.
authors.forename: Erika M
authors.initials: EM
authors.lastname: Young
authors.forename: Robert V
authors.initials: RV
authors.lastname: Considine
authors.forename: Fred R
authors.initials: FR
authors.lastname: Sattler
authors.forename: Mark A
authors.initials: MA
authors.lastname: Deeg
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Buchanan
authors.forename: Mikako
authors.initials: M
authors.lastname: Degawa-Yamauchi
authors.forename: Sudha
authors.initials: S
authors.lastname: Shankar
authors.forename: Hannah
authors.initials: H
authors.lastname: Edmondson-Melançon
authors.forename: Jaime
authors.initials: J
authors.lastname: Hernandez
authors.forename: Michael P
authors.initials: MP
authors.lastname: Dubé
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects; D002219:Carbamates; D004359:Drug Therapy, Combination; D005260:Female; D005342:Fibrinolysis / Q000276:immunology; D005663:Furans; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D017320:HIV Protease Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D019469:Indinavir / Q000009:adverse effects* / Q000627:therapeutic use; D007249:Inflammation / Q000097:blood / Q000276:immunology; D007333:Insulin Resistance / Q000276:immunology; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D018119:Stavudine / Q000009:adverse effects / Q000627:therapeutic use; D013449:Sulfonamides / Q000009:adverse effects* / Q000627:therapeutic use; D010959:Tissue Plasminogen Activator / Q000097:blood
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D002219:Carbamates; D005663:Furans; D017320:HIV Protease Inhibitors; D017395:Plasminogen Activator Inhibitor 1; D018894:Reverse Transcriptase Inhibitors; D013449:Sulfonamides; C095108:amprenavir; D019469:Indinavir; D018119:Stavudine; D010959:Tissue Plasminogen Activator