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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 26, No 2, March/April 2015
78
AFRICA
strated decreased lipid values by 11–25% in HIV-infected
patients. It is yet to be determined whether hyperlipidaemia
in HIV-infected subjects should be considered a separate
cardiovascular risk factor. In patients with carotid stenosis,
statins have reduced intimo-medial thickness and cerebro-
vascular events, and have beneficial anti-inflammatory and
pleiotropic properties.
77
It is unknown whether these effects
will materialise in HIV-infected patients beyond its lipid-
lowering potential.
•
The classic risk factors, including smoking, diabetes, hyper-
tension and hyperlipidaemia, are assuming greater signifi-
cance in the HIV population.
78
The atherosclerotic burden
may be worsened under these circumstances, particularly in
association with HAART. Patients should be counselled to
stop smoking. Psychological and medicinal measures should
be instituted, if indicated, together with medical optimisation
of diabetes and hypertension, as in HIV-naïve patients.
The SMART study
79
has shown that the risks outweigh the
benefits in subjects on prolonged HAART who have elevated
inflammatory markers. In addition, low CD4 counts were
associated with increased surrogate markers for atherosclerosis
and cardiovascular complications. Despite viral suppression,
residual immunological effects may still confer a cardiovascular
risk, which, in part, may be related to gut bacterial translocation.
79
Current therapeutic options that are being explored to negate
this adverse influence include novel therapies to modify T-cell
activation and senescence, immunomodulation, and nutritional
supplements to restore the gut flora. Although it is thought
that short-term HAART may reduce cardiovascular risk, it
is not known whether it will completely reverse HIV-related
cardiovascular disease in the long term.
Current challenges
The literature pertaining to the diverse spectrumof HIV-associated
large-vessel vasculopathy has been confined to case reports,
21,24,50,62,63
small patient series,
26,30
and larger studies
4,22,28,29,31,47,52,57-59
(Table 1).
The majority of caseloads have focused on clinical aspects of
aneurysmal and occlusive disease that were observed mainly
during the pre-HAART era, while, to date, the mechanisms
underlying the pathological process remain theoretical without
definitive isolation of an infective agent. Limitations in terms of
patient numbers, inconsistencies in respect of specimen sampling
for hypercoagulation, thrombophilic screens, histopathological
sampling and microbiological and viral analyses have resulted in
an incomplete understanding of HIV-associated vascular disease.
In future studies, attempts should be made to obtain
representative diseased and juxtaposed, apparently normal,
arterial wall samples to facilitate an improved understanding
of the established and evolving disease spectrum, respectively.
Furthermore, molecular microbiological techniques for
isolation and identification of infective organisms need ongoing
development and optimisation to keep abreast with emerging
technology.
Future directions
The vascular endothelium and smooth muscle cell components
are potential keys to unravelling some of the mysteries relating to
the pathophysiology and microscopic changes in HIV-associated
vasculopathy. Animal models such as the transgenic mice model
have been used to simulate arterial wall pathology following HIV
invasion. This seems promising for improved understanding of
the possible disease pathogenesis.
Various molecular markers and receptors are being studied
at a cellular level with the aim of blocking the destructive
biochemical pathways.
80
Furthermore the availability of
HAART, while offering a therapeutic solution, is not without its
metabolic adversities that fuel the atherogenic process, thereby
compounding risks. Newer agents with or without minimal
metabolic complications are being investigated.
Presently there are no universal surgical guidelines for
HIV-associated large-vessel vasculopathy. Surgical intervention
remains the mainstay of therapy for aneurysmal and occlusive
disease, however, with endovascular intervention reserved for a
subset of patients with poor physiological reserves or who are
too ill to tolerate anaesthesia. The exact role of endovascular
intervention for this profile of patients requires definition and
as yet there are no studies comparing surgery and endovascular
intervention in HIV-infected patients. The prevalence of
peripheral arterial disease in the HIV-positive population needs
further investigation as asymptomatic patients manifest with
subclinical atherosclerosis, as determined by deranged ABIs
following exercise.
81
Conclusion
HIV is a pandemic with a widespread disease profile. The
availability of HAART has offered a therapeutic lifeline for
longevity but is negated by potential vascular complications.
As a result the incidence of vasculopathic manifestations over
the last decade has increased. The challenge lies in unravelling
the elusive aetiological and histopathological mysteries that
surround HIV-associated large-vessel vasculopathy, and in so
doing, assist with improved insight and knowledge in devising
potential future therapeutic modalities that will enable improved
vascular surgical practice in this context.
Table 1. Literature review of HIV-associated
vasculopathy series
4,22,28-31,47-48,52,57-59
Publication
year
Aneurysms
Occlusive
disease
n
MR
(%)
n
MR
(%)
Marks and Kushov
28
1995
12 ND 0 N/A
Nair,
et al
.
29
1999
10 30
0 N/A
Nair,
et al
.
30
2000
4 25
0 N/A
Nair,
et al.
59
2000
0 N/A 22
0
Nair,
et al
.
31
2000
28
7
0 N/A
Van Marle,
et al
.
47
2002
9
0 24
0
Lin,
et al.
57
2004
20 33 28 15
Mulaudzi,
et al
.
22
2005
0 N/A 22 14
Botes and van Marle
48
2007
24 10.6 66 3.6
Van Marle,
et al
.
58
2009
0 N/A 91 20
Robbs and Paruk
4
2010
111
9 115 11
Padayachy and Robbs
52
2012
22 14
0 N/A
MR: mortality rate;
n
: patient numbers; N/A: not applicable; ND: not
documented, %: patient percentage.