CARDIOVASCULAR JOURNAL OF AFRICA • Vol 22, No 3, May/June 2011
134
AFRICA
Is HIV-1 infection associated with endothelial dysfunction
in a population of African ancestry in South Africa?
C FOURIE, J VAN ROOYEN, M PIETERS, K CONRADIE, T HOEKSTRA, A SCHUTTE
Abstract
The chronic infection status suffered by HIV-infected indi-
viduals promotes chronic arterial inflammation and injury,
which leads to dysfunction of the endothelium, atherosclero-
sis and thrombosis. Although HIV-1 subtype C is prevalent
in South Africa and accounts for almost a third of the infec-
tions worldwide, this subtype differs genetically from HIV-1
subtype B on which the majority of studies have been done.
The objective of this study was to assess whether newly iden-
tified, never-treated, HIV-1-infected South African partici-
pants showed signs of endothelial dysfunction, accelerated
atherosclerosis and increased blood coagulation.
We compared 300 newly diagnosed (never antiretroviral-
treated) HIV-infected participants to 300 age-, gender-, body
mass index- and locality-matched uninfected controls. Levels
of high-density lipoprotein cholesterol (HDL-C), triglycer-
ides, interleukin-6 (IL-6), C-reactive protein (CRP), intercel-
lular adhesion molecule-1 (ICAM-1), vascular cell adhesion
molecule-1 (VCAM-1), fibrinogen and plasminogen activa-
tor inhibitor-1 (PAI-1), and carotid radialis pulse wave veloc-
ity (cr-PWV) were determined. The HIV-infected partici-
pants showed lower HDL-C and higher IL-6, CRP, ICAM-1
and VCAM-1 levels compared to the uninfected controls. No
differences in fibrinogen and PAI-1 levels were detected. A
continuous positive trend of increasing age with cr-PWV was
detected in the HIV-infected group.
Our findings suggest inflammatory injury of the endo-
thelium, pointing to endothelial dysfunction of never-treated
HIV-1-infected South Africans of African ancestry. Although
no indication of a prothrombotic state could be detected,
there was an indication of accelerated vascular aging and
probable early atherosclerosis in the older HIV-infected
participants.
Keywords:
HIV-1, South Africa, endothelial dysfunction, vascu-
lar aging, never treated, inflammation
Submitted 12/2/10, accepted 12/7/10
Cardiovasc J Afr
2011;
22
: 134–140
DOI: CVJ-21.049
Several cardiovascular risk factors have been associated with
or seen in the human immunodeficiency virus (HIV)-infected
population since the trend of longer life expectancy due to
antiretroviral (ARV) therapy.
1,2
Worldwide, various forms of
cardiovascular involvement, such as endothelial dysfunction,
3
accelerated atherosclerosis
4
and coagulation disorders
5
have been
documented among HIV-infected individuals. In South Africa,
atherosclerotic disease, historically not common in most black
Africans, is increasing.
6
One of the important contributors, at
least in part, to this increase could be the cardiac complications
related to HIV infection, as South Africa is the country with the
highest number of HIV infections in the world.
7
The chronic infection of HIV-infected individuals promotes
chronic arterial inflammation and injury, which in turn, promotes
dysfunction of the endothelium, atherosclerosis and thrombo-
sis.
5,8
Endothelial injury and dysfunction have been proposed as
plausible links between HIV infection and atherosclerosis.
9
The
development of atherosclerosis may be the consequence of infec-
tion-triggered endothelial damage,
10
and atherosclerotic cardio-
vascular events are commonly manifested via thrombotic events.
11
Increased levels of the inflammatory markers C-reactive
protein (CRP), interleukin 6 (IL-6),
8
and cell adhesion mole-
cules, intercellular adhesion molecule-1 (ICAM-1) and vascular
cell adhesion molecule-1 (VCAM-1)
3
have been reported in the
HIV-infected population.
2,12
Accelerated atherosclerosis has also
been detected in HIV-infected patients,
1,13
and a wide range of
coagulation disordersmay be associatedwithHIV infection itself.
5
Although an estimated 5.5 million people are living with
HIV in South Africa
7
where HIV-1 subtype C prevails,
14,15
the
majority of studies on HIV have been done on HIV-1 subtype B,
which is responsible for infections in North America, Europe and
Australia.
15,16
Subtype C accounts for 55 to 60% of all HIV infec-
tions worldwide and differs as much as 30% in its genome from
subtype B.
17,18
The clinical consequences of subtype variations
are still unknown and the effect of the HIV-1 subtype C virus on
the vascular system is not certain.
Recently it has been recommended that HIV infection
per se
should count as a coronary risk factor, similar to the traditional
cardiovascular risk factors (smoking, hypertension, hypercholes-
terolaemia and diabetes).
4
Although data of Lorenz
et al.
support
the hypothesis that HIV infection promotes early atherosclerosis
independently of the ‘classical’ vascular risk factors,
13
the role
of HIV infection as a risk factor for premature atherosclerosis is
still controversial.
9,19
There is also uncertainty about the relative
contribution of the viral infection, the virus itself, the associated
inflammatory response, antiretroviral therapy, and the interac-
tion between them and the cardiovascular risk factors seen in the
HIV-infected population.
20,21
In view of the above, the aim of this study was to assess wheth-
er newly identified, never-treated, HIV-1-infected South Africans
of African ancestry showed signs of endothelial dysfunction,
accelerated atherosclerosis and increased coagulation, which
could lead to thrombosis.
HART (Hypertension in Africa Research Team), Physiology,
North-West University, Potchefstroom, South Africa
C FOURIE, PhD,
J VAN ROOYEN, DSc
A SCHUTTE, PhD
TReNDS Centre of Excellence – Nutrition, North West
University, Potchefstroom, South Africa
M PIETERS, PhD
K CONRADIE, PhD
Julius Centre for Health Sciences and Primary Care,
University Medical Centre Utrecht, Utrecht, the Netherlands
T HOEKSTRA, PhD
