Hypofibrinolytic state in HIV-1-infected patients treated with protease inhibitor-containing highly active antiretroviral therapy.
Decreased insulin sensitivity, hyperlipidemia, and body fat changes are considered as risk factors for coronary heart disease (CHD). A clustering of such factors (metabolic syndrome [MSDR]) exponentially increases the risk. Impaired fibrinolysis and increased coagulation are additional independent risk factors for CHD. We studied the effects of protease inhibitor (PI)-containing highly active antiretroviral therapy (HAART) on metabolic and hemostatic parameters in 363 HIV-infected individuals, of whom 266 were receiving PI-containing HAART and 97 were treatment naive. The fasting plasma levels of insulin, glucose, triglycerides, cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, plasminogen activator inhibitor type 1 (PAI-1), and fibrinogen were evaluated together with the areas of visceral adipose tissue and the visceral adipose tissue/subcutaneous adipose tissue area ratio. The levels of insulin, triglycerides, cholesterol, and low-density lipoprotein cholesterol; visceral adipose tissue area; low-density lipoprotein/high-density lipoprotein ratio; and visceral adipose tissue/subcutaneous adipose tissue area ratio were significantly increased in patients receiving PI-containing HAART compared with treatment-naive patients. The levels of PAI-1 and fibrinogen were significantly higher in patients receiving PI-containing HAART. PAI-1 levels were higher in individuals with MSDR but also in patients without MSDR who were receiving PI-containing HAART. PAI-1 was independently correlated to use of PI-containing HAART, triglyceride level, insulin level, and body mass index (p <.001). These findings suggest that patients receiving PI-containing HAART have decreased fibrinolysis and increased coagulability, which may thus represent additional risk factors for cardiovascular disease in this patient group.
Koppel
Kristina
K
Venhälsan (Gay Men's Health Clinic), Karolinska Institute, Söder Hospital Stockholm, 118 83 Stockholm, Sweden. kristina.koppel@venh.sos.sll.se
Bratt
Göran
G
Schulman
Sam
S
Bylund
Håkan
H
Sandström
Eric
E
D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D001786:Blood Glucose; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000209:etiology; D005340:Fibrinogen / Q000032:analysis*; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000009:adverse effects*; D006801:Humans; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008060:Lipodystrophy / Q000209:etiology; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D012307:Risk Factors
D001786:Blood Glucose; D017320:HIV Protease Inhibitors; D008055:Lipids; D017395:Plasminogen Activator Inhibitor 1; D005340:Fibrinogen; D002097:C-Reactive Protein