title: The effect of initiating combined antiretroviral therapy on endothelial cell activation and coagulation markers in South African HIV-infected individuals.
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.
authors.affiliation: Department of Internal Medicine, Slotervaart Hospital, Amsterdam, the Netherlands. jong.eefje@gmail.com
authors.forename: Eefje
authors.initials: E
authors.lastname: Jong
authors.forename: Susan
authors.initials: S
authors.lastname: Louw
authors.forename: Eric C M
authors.initials: EC
authors.lastname: van Gorp
authors.forename: Joost C M
authors.initials: JC
authors.lastname: Meijers
authors.forename: Hugo
authors.initials: H
authors.lastname: ten Cate
authors.forename: Barry F
authors.initials: BF
authors.lastname: Jacobson
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation / Q000187:drug effects*; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D004359:Drug Therapy, Combination; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D015658:HIV Infections / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008137:Longitudinal Studies; D035002:Lower Extremity / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011486:Protein C / Q000378:metabolism; D017293:Protein S / Q000378:metabolism; D013019:South Africa; D013997:Time Factors; D016896:Treatment Outcome; D014463:Ultrasonography; D020246:Venous Thrombosis / Q000097:blood* / Q000000981:diagnostic imaging / Q000276:immunology / Q000821:virology; D019562:Viral Load; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D044966:Anti-Retroviral Agents; D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D011486:Protein C; D017293:Protein S; C036309:fibrin fragment D; D014841:von Willebrand Factor