Cardiovascular Journal of Africa: Vol 30 No 2 (March/April 2019)

CARDIOVASCULAR JOURNAL OF AFRICA • Volume 30, No 2, March/April 2019

AFRICA

The cardiovascular effects of

Aspalathus linearis

supplementation in male Wistar rats receiving fixed-dose

combination first-line antiretroviral therapy

I Webster, EG Imperial, C Westcott, H Strijdom

Abstract

HIV-infected populations receiving antiretroviral therapy

(ART) have an increased risk of cardiovascular disease. The

beneficial cardiovascular effects of rooibos are well described;

however, it is unknown whether rooibos ameliorates harmful

ART-induced cardiovascular side effects. We investigated

the cardiometabolic effects of rooibos co-treatment in rats

receiving ART (efavirenz, emtricitabine, tenofovir) for nine

weeks. Rooibos treatment reduced total cholesterol levels;

however, triglyceride, phospholipid and thiobarbituric acid-

reactive substance levels were unaffected by ART, rooibos or

combination treatment. In isolated hearts exposed to ischae-

mia–reperfusion injury, ART resulted in increased infarct

sizes compared to controls, which was not observed when

co-treated with rooibos. Vascular studies showed reduced

aortic relaxation with ART, and improved relaxation when

co-treated with rooibos. In conclusion, we show that rooi-

bos treatment reduced total cholesterol levels in control

rats, and that rooibos co-treatment ameliorated the harmful

ART-induced cardiovascular effects. These findings are novel

and warrant further studies into underlying mechanisms and

clinical relevance.

Keywords:

HIV, antiretrovirals, cardiovascular,

Aspalathus line-

aris,

vascular reactivity

Submitted 27/7/18, accepted 10/12/18

Published online 7/2/19

Cardiovasc J Afr

2019;

: 95–102

www.cvja.co.za

DOI: 10.5830/CVJA-2018-075

Highly active antiretroviral therapy (HAART) was introduced

in 1996 to target the replication and spread of the human

immunodeficiency virus (HIV).

These drug combinations

have become very effective and now comprise three or more

drugs in a single tablet.

2,3

The effectiveness of HAART is

evidenced in the decreased rate of HIV-related mortalities since

its introduction.

In South Africa, particularly, an increased

roll-out of antiretroviral drugs in 2005 was associated with a

significant decline in AIDS-related deaths in the short term.

ART, especially the protease inhibitor (PI) class, has been

associated with increased cardiovascular complications; however,

findings remain contradictory and more studies are needed for it

to be conclusive.

4-6

In 2012 the South African Department of Health approved

the use of a new first-line ART consisting of the nucleoside

reverse transcriptase inhibitors (NRTIs): tenofovir diphosphate

(TDF) and emtricitabine 5

′

-triphosphate (FTC), and the

non-nucleoside reverse transcriptase inhibitor (NNRTI),

efavirenz (EFV), in a single-tablet fixed-dose combination

(FDC).

Studies investigating the long-term effects of this

specific FDC are sparse. South Africa (SA) currently has the

largest ART roll-out programme in the world and in 2016

became the first African country to implement pre-exposure

prophylaxis (PrEP), specifically in the form of TDF or the

combination of TDF/FTC, as a preventative treatment given to

HIV-negative people.

The importance of extensive research into

the long-term cardiovascular effects of the current first-line FDC

ART regimen is, therefore, undeniably high. Not only is this

research fundamental, but further extrapolations into the exact

mechanisms and possible co-treatments will aid in the on-going

battle against HIV/AIDS.

Prolonged use of HAART has been associated with toxicity

and a number of detrimental effects on the body, including

nephrotoxicity and lipodystrophy.

9,10

Furthermore, previous studies

have linked the long-term use of ART to myocardial infarctions

(MI) and increased risk of developing cardiovascular disease

(CVD).

1,11,12

This may be caused by the HIV infection itself,

the

immunological responses to the virus, or by the effects of HAART

through its effects on both lipid and glucose metabolism.

Reactive oxygen species (ROS) and oxidative stress have also

been identified as key role players in the pathogenesis of CVDand

an important precursor of CVD, endothelial dysfunction (ED).

ED encompasses diminished production/availability of nitric

oxide and/or a disparity in the endothelium-derived relaxing and

contracting factors, which can lead to impaired endothelium-

dependent vasodilatation.

14,15

Viral infections, energy deprivation,

oxidative stress or calcium depletion in the endoplasmic

reticulum are known to induce an inflammatory response, which

can result in ED.

14,15

The development of ED has been associated

with protease inhibitor-induced toxicity in isolated vasculature

models in particular; furthermore, subsequent CVD and long-

term (18 months) FDC ART treatment have also been associated

with decreased endothelial function, as measured by percentage

flow-mediated dilatation (FMD%).

16-18

Antioxidants counter excessive ROS generation and the

development of oxidative stress.

Aspalathus linearis

, commonly

known as rooibos, is a well-established source of antioxidants.

It is a plant that is indigenous to SA and its stems and

Division of Medical Physiology, Faculty of Medicine and

Health Sciences, University of Stellenbosch, Cape Town,

South Africa

I Webster, PhD,

iwebster@sun.ac.za

EG Imperial, MSc

C Westcott, PhD

H Strijdom, MB ChB, PhD