Hypofibrinolytic State in HIV-1–Infected Patients Treated With Protease Inhibitor–Containing Highly Active Antiretroviral Therapy

Abstract

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.

Is HIV-1 infection associated with endothelial dysfunction in a population of African ancestry in South Africa?

“…Endothelial dysfunction is also associated with a prothrombotic state,44 and studies which investigated the prothrombotic state in HIV-infected populations showed increased levels of PAI-1 activity and fibrinogen 4,45,46. However, in our study neither the PAI-1 activity nor fibrinogen levels were increased in the HIV-infected subjects, indicating no signs of a prothrombotic state.…”

Risk of premature atherosclerosis and ischemic heart disease associated with HIV infection and antiretroviral therapy

“…3,4 Besides, some data suggest that endothelial dysfunction, impaired fibrinolysis, and excess inflammation are more common in HIV-positive patients than in general population, and may contribute to an increased cardiovascular risk. 5 At the same time, carotid intimal-media thickness and coronary calcification assessments suggest increased incidence of atherosclerotic disease and premature occurrence of arterial atherosclerotic lesions among HIV-infected individuals. 6 Finally, recent reports raise the suspicion that combination antiretroviral therapy may also induce arterial hypertension, 7e9 even though a few comparative studies on blood pressure in HIV-positive subjects have been reported still today.…”

HIV-Infektion, antiretrovirale Therapie und Endothel

“…Bezüglich des Effekts auf Adhäsionsmoleküle sind die Daten nicht konklusiv [12,42,68]. Zwei Studien haben gar eine Erhöhung von PAI-1 gezeigt [12,36]. Zum Entzündungsmarker CRP, der prognostische Bedeutung besitzt und einen direkten Zusammenhang mit der Endothelfunktion hat, gibt es nur sehr limitierte Untersuchungen bei HIV-infizierten Abbildung 3.…”