The association of HIV infection with plasma clot characteristics in black South Africans

Abstract

INTRODUCTION AND AIM - Human immunodeficiency virus (HIV) infection is still one of the largest burdens to the world's health, and South Africa reportedly has the highest prevalence in the world. HIV, as well as antiretroviral therapy (ART) are associated with hypercoagulability, consequently increasing thrombotic risk. One of the main components of hypercoagulability is altered clot properties, which contribute to thrombosis-related cardiovascular complications, as the clots with tightly packed thin fibrin structures tend to be more prothrombotic. It is hypothesised that one of the mechanisms through which HIV-infected patients' thrombotic risk is increased is via altered clot structure. Therefore, the current study aimed to investigate the association of HIV status and ART respectively, with fibrinogen concentration and plasma clot properties in a sub-group of participants from the South African, North West Province arm of the PURE study. PARTICIPANTS AND METHODS - The study made use of data collected in 2005 and 2010 in the South African North West Province arm of the international Prospective Urban and Rural Epidemiology (PURE-SA-NW) study. The study included data from 151 newly infected HIV-positive participants at baseline, 70 of whom were receiving ART by 2010 and 81 who were still untreated. These participants were systematically matched to 176 HIV-uninfected individuals. Total and ' fibrinogen concentration, as well as fibrin clot properties obtained with turbidimetry, were cross-sectionally compared at baseline between HIV-infected and HIV-uninfected participants, and between the HIV-treated, the untreated and HIV-uninfected groups at the 2010 follow-up. Prospective comparisons, over the five-year period, were furthermore made within and between these groups. RESULTS - At baseline, HIV-infected individuals presented with lower total fibrinogen concentration and higher percentage y' fibrinogen compared with the controls. Plasma clots from these participants were less dense (lower maximum absorbance), but took longer to lyse than those of the HIV-uninfected participants. At the 2010 follow up, the HIV-treated and untreated groups did not differ regarding the outcome variables, but differed compared to the HIV-uninfected group. Both HIV-infected groups presented with lower total fibrinogen and maximum absorbance compared to the HIV-uninfected group, with the treated group also presenting with longer clot lysis times (CLT) than the HIV-uninfected group. Prospectively, from baseline to follow-up, fibrinogen increased (or tended to) in all three groups, with y' fibrinogen decreasing in all three groups. The rate of lateral aggregation (slope) and maximum absorbance (clot density) increased in all three groups, with a borderline slope increase in the treated group. CLT increased significantly over the 5-year period in the HIV-treated and HIV-uninfected groups, but not in the untreated group. A significant difference in the extent of change over time, was also observed for lag time, which decreased more in the HIV-treated group. The age-related progression to formation of more prothrombotic clots was somewhat delayed in the HIV untreated group, while ART use seemed to counteract this "protective" effect. CONCLUSION - The study showed HIV-infection to be associated with lower total fibrinogen concentration and maximum absorbance compared to HIV-uninfected participants. The cross-sectional comparisons also found HIV infection to be associated with longer CLT, which could relate to altered levels of other variables affected by the HIV status, such as LDL-C, rather than to altered plasma clot structure. Prospectively, over the five-year period, HIV-infection demonstrated a tendency to delay the age-associated progression to more prothrombotic clot properties, but ART treatment partly neutralised this "protective effect."