[Show abstract][Hide abstract] ABSTRACT: An increased incidence of venous thromboembolism (VTE) is observed in human immunodeficiency virus (HIV)-infected patients. Only a limited number of studies described the effect of combined antiretroviral therapy (cART) on coagulation markers. In a prospective cohort study in cART-naive South African HIV-infected individuals the effect of initiating cART on markers of endothelial cell activation, coagulation and natural anticoagulation was studied. These markers were compared to the reference ranges for an HIV-uninfected control population recruited from hospital staff. A venous ultrasound of both legs was performed to detect asymptomatic deep venous thrombosis (DVT). A total number of 123 HIV-infected participants were included. The patients were predominantly black and severely immuno-compromised. The CD4 cell count increased and the HIV viral load decreased significantly after the initiation of cART (p<0.001). The median follow-up period was 7.2 (± 1.6) months. Laboratory testing before and after initiation of cART was completed by 86 patients. Before initiating cART significantly elevated von Willebrand factor and D-dimer levels, increased activated protein C sensitivity ratio (APCsr) and decreased total and free protein S and protein C levels were observed compared to HIV-negative controls. At follow-up all markers, except APCsr, improved towards the normal range for controls without showing complete normalisation. In a subgroup of 57 patients no asymptomatic DVT was found. Compared to the controls, abnormal levels of coagulation markers were observed in HIV-infected individuals before and after the initiation of cART. Most markers improved after starting cART, but remained significantly different from the controls, indicating a persistent disturbed haemostatic balance.
Thrombosis and Haemostasis 09/2010; 104(6):1228-34. · 5.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The incidence of arterial and venous thrombosis in HIV-infected patients is increased compared to healthy controls. In this cross-sectional analysis we measured markers of endothelial cell activation, thrombin generation, fibrinolysis and anticoagulation combined with endogenous thrombin potential (ETP) and activated protein C sensitivity ratio (APCsr) as more global markers. We included 160 consecutive HIV-infected patients with a median age of 46 years (range, 27-77), of whom 92% were male, 74% Caucasian, 11% African American, 9% Hispanic, and 6% Asian. Homosexual contact was the main transmission mode. Seventy percent of patients were using combined antiretroviral therapy (cART). In 83% of patients laboratory markers outside the normal range for a non-HIV-infected population were observed. Significant lower levels of von Willebrand factor (vWF; p = 0.03), factor VIII (p < 0.0001), D-dimer (p = 0.01), and ETP (p = 0.01) were observed in HIV-infected patients on cART compared to patients not on cART. Significant lower levels of protein C (p = 0.05) and free protein S (p < 0.0001), and increased APCsr (p < 0.0001) were found in the HIV-infected patients not on cART. A single association was observed between raised levels of fibrinogen and use of a protease inhibitor (p = 0.002). No significant difference was observed in the percentage of patients with laboratory markers outside the normal range between patients using cART-regimens containing abacavir, stavudine, or didanosine and those with other nucleoside reverse transcriptase inhibitors. Although the prevalence of coagulation abnormalities was lower in HIV-infected patients using cART, a considerable proportion of HIV-infected patients on cART show endothelial cell activation and increased APCsr, suggestive of a persistent procoagulant state.
AIDS patient care and STDs 11/2009; 23(12):1001-7. · 2.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Abnormalities that predispose to a hypercoagulable state with an increased incidence of venous thrombosis have been described in human immunodeficiency virus (HIV) infections and are associated with an increased mortality. A recent systematic review by Klein et al concluded that further studies are essential to elucidate the link between HIV infection and deep vein thrombosis (DVT). We prospectively evaluated 24 consecutive, active people presenting with an acute DVT; 13 consented to HIV testing, revealing an HIV prevalence of 84% (95% confidence interval [CI], 0.65-1.04). In a matched healthy control group, the HIV prevalence was 4% (95% CI, 0.039-0.041). The high HIV prevalence in the DVT group that consented to testing was also significantly higher compared to that in the South African population, estimated to be 10% in 2005. Although the study numbers were low, a statistically significant increased prevalence of HIV infection was found in patients with acute DVTs.
Clinical and Applied Thrombosis/Hemostasis 08/2008; 14(3):352-5. · 1.58 Impact Factor