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

CARDIOVASCULAR JOURNAL OF AFRICA • Volume 29, No 3, May/June 2018

160

AFRICA

Danish cohort of virally suppressedHIV-patients versus controls.

In the Graham report among Kenyan women, E-selectin levels

were unchanged at 12 months compared to baseline.

We believe

our report of a lack of difference in E-selectin levels by HIV

status to be the first in SSA. The Graham and Danish cohort

reports suggest that HIV may not be as strongly associated with

E-selectin, compared to VCAM-1 or ICAM-1 levels.

Our findings of a lack of association between IL-6 level and

cIMT with endothelial dysfunction are similar to those of Fourie

et al.

in their study among virally suppressed black South African

patients.

Our findings and those of Fourie

et al.

in this context

do not align with the observation among non-African patients

that IL-6 level and cIMT were associated with endothelial

injury.

8,26,30

Our small sample size may have precluded our ability

to detect these associations in our setting.

Of note, observations of this association in non-African

cohorts have not always been consistent. In a recent prospective

study of ART-naïve HIV-infected adults in the USA, ICAM-1

level was not associated with progression in cIMT.

More studies

are required to establish the contribution of traditional CVD

risk factors to endothelial dysfunction among virally suppressed

HIV-infected patients in SSA, and to explore novel markers that

may explain the proportion of risk not conferred by traditional

CVD risk factors.

The relationship between sCD163 level and biomarkers of

endothelial dysfunction has not been reported in SSA. Our results

of a lack of association between sCD163 and VCAM-1 have

been reported by some,

but not all

studies in non-SSA settings

among patients on ART. We had expected a positive association

between sCD163 and VCAM-1 in our study because sCD163

induces arterial inflammation, which may lead to increased

shedding of VCAM-1.

We observed an unexpected negative

association between sCD163 with I-CAM and E-selectin levels.

We are cautious in interpreting the negative associations observed

between sCD163 with ICAM-1 and E-selectin levels in our study

pending assessment of these associations in similar cohorts.

Limitations

The main limitations of our study are the cross-sectional design,

small sample size and limited number of biomarkers that were

studied. The cross-sectional design precludes the ability to arrive

at a temporal association between our predictors and outcomes.

Furthermore, studying activated peripheral blood mononuclear

cells and human endothelial cells would provide a more robust

understanding of pathways involved in the development of

endothelial dysfunction. Because we relied on standard-of-

care HIV RNA results that were measured within an average

of three months prior to time of enrolment, it is possible that

some patients may have been viraemic. We believe that this

potential effect would have been minimal, given the high viral

suppression rates of 96.5% observed among patients on ART in

routine HIV care in Botswana.

A strength of our study was the

ascertainment of traditional CVD risk factors, which allowed for

robust assessment of confounding.

Conclusion

We observed that 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. Unexpectedly, we observed a modest inverse

relationship between sCD163 level (a marker of monocyte

activation) and some biomarkers of endothelial dysfunction.

Our study is the first to report on markers of endothelial

dysfunction following prolonged ART among virally suppressed

black Africans. We also report a lack of association between

sCD163 and VCAM-1 for the first time in a SSA clinical

cohort, replicating what has been observed in non-African

cohorts, and we corroborate a previously demonstrated lack of

association between IL-6 and cIMT with endothelial dysfunction

in this setting. Future work should explore the 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.

The study was funded by the National Institutes of Health (NIH), grant

NIH/NIAID 5P30AI060354-0 through Harvard University Centre for

AIDS Research (HU-CFAR), Harvard Global Health Institute (HGHI),

grant BWH#2013D002079, International Fogarty Training grant (PI-Max

Essex DVM, Botswana–Harvard AIDS partnership) and NIH/NHLBI

R01HL132786 (to VAT).

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