Cardiovascular Journal of Africa: Vol 29 No 3 (May/Junel 2018)

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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 29, No 3, May/June 2018 AFRICA 155
HIV disease is associated with increased biomarkers
of endothelial dysfunction despite viral suppression on
long-term antiretroviral therapy in Botswana
Mosepele Mosepele, Terence Mohammed, Lucy Mupfumi, Sikhulile Moyo, Kara Bennett, Shahin Lockman,
Linda C Hemphill, Virginia A Triant
Abstract
Background: Untreated HIV infection is associated with
increased biomarkers of endothelial dysfunction. However,
the predictors and degree of endothelial dysfunction among
virally suppressed HIV-infected adults on long-term antiret-
roviral therapy (ART) have not been well studied in sub-
Saharan Africa (SSA).
Methods: We enrolled 112 HIV-infected adults with viro-
logical suppression on long-term ART and 84 HIV-uninfected
controls in Botswana. We measured plasma levels of markers
of endothelial injury [soluble vascular adhesion molecule 1
(VCAM-1), intercellular adhesion molecule 1 (ICAM-1) and
E-selectin] and plasma levels of biomarkers of inflammation
[interleukin 6 (IL-6)] and monocyte activation (sCD163).
Baseline traditional cardiovascular disease (CVD) risk factors
and bilateral common carotid intima–media thickness (cIMT)
were also available for all participants. We assessed whether
HIV status (despite virological suppression on ART) was
associated with biomarkers of endothelial dysfunction after
controlling for traditional CVD risk factors in linear regression
models. We additionally assessed the association between
IL-6, sCD163 and cIMT with endothelial dysfunction in
separate multivariate linear regression models, controlling for
cIMT, among virally suppressed HIV-infected participants
only.
Results: In multivariate analysis, HIV infection was signifi-
cantly associated with increased VCAM-1 (p < 0.01) and
ICAM-1 (p = 0.03) but not E-selectin (p = 0.74) levels. Within
the HIV-positive group, higher sCD163 levels were associ-
ated with decreased ICAM-1 and E-selectin (p < 0.01 and p
= 0.01, respectively) but not VCAM-1 (p = 0.13) levels. IL-6
was not associated with any of the biomarkers of endothelial
dysfunction.
Conclusion: HIV disease was associated with biomarkers of
endothelial dysfunction among virally suppressed adults in
Botswana on long-term ART after controlling for traditional
CVD risk factors. Future work should explore the clinical
impact of persistent endothelial dysfunction following long-
term HIV viral suppression on the risk of CVD clinical
endpoints among HIV-infected patients in this setting.
Keywords: human immune deficiency virus, endothelial dysfunc-
tion, inflammation, monocyte activation, atherosclerosis, Africa,
cardiovascular disease
Submitted 12/1/17, accepted 14/1/18
Published online 14/5/18
Cardiovasc J Afr 2018; 29: 155–161
DOI: 10.5830/CVJA-2018-003
Biomarkers of endothelial dysfunction are elevated among
untreated HIV-infected patients in Africa,1-4 and have been noted
to be persistently elevated among non-African HIV-infected
patients after initiating antiretroviral therapy (ART).5-8 However,
little is known about endothelial dysfunction among virally
suppressed HIV-infected patients following long-term ART
versus controls in the African setting. Similarly, the independent
effects of chronic inflammation and monocyte activation on
endothelial dysfunction have not been widely assessed among
African patients following sustained viral suppression.
Increased expression of endothelial adhesion molecules
is a marker of endothelial dysfunction. Commonly studied
endothelial adhesion molecules that predict atherosclerotic
disease in the general population include intercellular adhesion
molecule 1 (ICAM-1), vascular cell adhesion molecule 1
(VCAM-1) and selectins (P- or E-selectin).9-11 These molecules
Department of Medicine, Faculty of Medicine, University of
Botswana, Gaborone, Botswana
Mosepele Mosepele, MD, MSc,
Botswana–Harvard AIDS Institute Partnership, Gaborone,
Botswana
Mosepele Mosepele, MD, MSc
Terence Mohammed, MSc
Lucy Mupfumi, MSc
Sikhulile Moyo, PhD
Shahin Lockman, MD, MSc
Bennett Statistical Consulting Inc, Ballston Lake, New
York, USA
Kara Bennett, MSc
Division of Infectious Diseases, Brigham and Women’s
Hospital, Boston, MA, USA
Shahin Lockman, MD, MSc
Department of Immunology and Infectious Diseases,
Harvard TH Chan School of Public Health, Boston, MA, USA
Shahin Lockman, MD, MSc
Division of Cardiology, Massachusetts General Hospital
and Harvard Medical School, Boston, MA, USA
Linda C Hemphill, MD
Division of General Internal Medicine and Division of
Infectious Diseases, Massachusetts General Hospital and
Harvard Medical School, Boston, MA, USA
Virginia A Triant, MD, MPH