Follow-up of thrombophilia, inflammation and markers of cardiovascular disease of HIV-1 patients on longterm cART

Epidemiological studies have demonstrated that people living with hiv have an
increased risk of developing venous thrombosis and cardiovascular disease than
the general population. The pathophysiology of thrombosis is a complex and
multifactorial process, in which the balance of procoagulant and anticoagulant
activity is disturbed causing a thrombophilic state. Several factors in
hiv-infection contribute to a procoagulant state. Earlier studies have
demonstrated a decrease in anticoagulant factors, e.g. protein S en C, and an
increase in procoagulant factors, e.g. D-dimer, fibrinogen and von Willebrand
factor (vWF). However, the pathophysiology of this thrombophilic state in
hiv-infection remains to be elucidated. Several studies have demonstrated that
the thrombotic risk in hiv-infection is associated with chronic
immune-activation and inflammation. On the other hand, combination
antiretroviral therapy (cART) is also associated with an increased risk of
venous thrombosis and cardiovascular disease. Both the hiv-infection itself and
its treatment could contribute to the thrombophilic state seen in hiv-infected
patients.
In 2010, the INF-BEAST study was performed to evaluate the effect of cART in
cART-naive hiv-infected. At start of cART, elevated levels of procoagulant
factors and cardiovascular markers (i.e. the lipid profile) with decreased
levels of anticoagulant factors were found. After a year of cART, a subtle
decrease in procoagulant factors and cardiovascular markers was seen with an
increase in anticoagulant factors. However, currently no data is available on
the long-term effect of cART on the thrombophilic state in hiv patients. In
this study we aim to determine the thrombophilic state and cardiovascular
markers in the INF-BEAST patient population after almost eight years of
treatment with cART.

1) to evaluate the effect of cART on markers of thrombophilia plasmalevels in
hiv-infected patients
2) to evaluate the long-term effect of cART on lipid spectrum
3) to evaluate the incidence of venous thrombosis and cardiovascular events in
hiv-infected patients on longterm cART.

A prospective cohort study

Patients who participated in the INF-BEAST study in 2010 will be re-invited for
the INF-BEAST2 study. After giving informed consent, the participant will be
invited once for the study procedures. First, a standardized questionnaire will
be conducted regarding medical history, risk factors for venous thrombosis,
cardiovascular disease and medication use. This will take ten to fifteen
minutes. Secondly, one peripheral venous puncture will be performed in order to
sample blood. The sampling of blood for this study will be combined with
routine follow-up blood testing necessary for the hiv-treatment as much as
possible in order to avoid extra punctures. An extra 12 mL will be sampled. The
study visit will be combined with routine follow-up appointments at the
department of Infectious Diseases or other specialists in the UMCG, as much as
possible. However, not all participants of the INF-BEAST study are still in
follow-up at the UMCG. For these patients participation to this study might
mean an extra visit and venous puncture.
The participants will not benefit from participation to this study, neither
will they be exposed to any risks as no risks are known from sampling an 12 mL
extra blood via venous puncture.