Pre-clinical carotid atherosclerosis and sCD163 among virally suppressed HIV patients in Botswana compared with uninfected controls

Abstract

ObjectivesHuman immune deficiency virus (HIV) is associated with increased cardiovascular disease (CVD) risk, yet the relationship between HIV and carotid atherosclerosis / monocyte activation among virally suppressed HIV-infected patients in sub-Saharan Africa is not well understood.MethodsWe measured traditional CVD risk factors, bilateral distal common carotid intima media thickness (cIMT), presence of carotid plaque and plasma sCD163 levels among virally suppressed HIV-infected adults and HIV-uninfected controls, in a cross-sectional study in Gaborone, Botswana. The associations between HIV status, traditional CVD risk factors, sCD163 and outcome of cIMT were assessed in univariate and multivariate linear regression models.ResultsWe enrolled 208 HIV-infected adults (55% Female, mean age 39 years) who had undetectable HIV-1 RNA on antiretroviral therapy and 224 HIV-uninfected controls (47% Female, mean age 37 years). There was no difference in cIMT between study groups, with mean cIMT 0.607mm and 0.599mm in HIV-infected and HIV-uninfected, respectively (p = 0.37). Plasma sCD163 was significantly higher in HIV-infected versus HIV-uninfected persons (1917ng/ml vs 1593ng/ml, p = 0.003), but was not associated with cIMT (p = 0.43 among all, p = 0.72 for HIV-infected only). In the final multivariate model, increased cIMT was associated with older age, being treated for hypertension, and higher non-HDL cholesterol among all (p<0.001, p = 0.03, p<0.001 respectively), and with older age and waist-hip ratio in HIV-infected participants (p = 0.02 & p = 0.02 respectively). Carotid plaque was present in a significantly higher proportion of HIV-infected adults (RR 2.15, 95% CI 1.22, 3.81).ConclusionsHIV-infected participants aged 30–50 years who have achieved viral suppression did not have increased cIMT when compared to HIV-uninfected controls in Botswana. However, well-controlled HIV was associated with excess monocyte activation. Future work should explore the impact of subclinical atherosclerosis on CVD events among HIV-infected and -uninfected adults in Botswana.

Prevalence and risk of subclinical carotid atherosclerosis in the global population with HIV: a systematic review and meta-analysis

“…Fourteen studies were conducted from Europe, 20,22–26,30,31,34,35,39,41–43 followed by America (4 studies), 10,27,28,38 Asia (4 studies), 11,21,29,32 and Africa (4 studies). 33,36,37,40 There are four studies using CIMT ≥ 0.78 mm criteria, 32,36,37,40 eight studies with CIMT ≥ 0.80 mm, 10,22,27,28,30,31,34,35 10 studies with CIMT ≥ 0.90 mm, 11,21,23–26,38,41,43 and four studies with CIMT ≥ 75th. 20,29,33,39…”

“…33,36,37,40 There are four studies using CIMT ≥ 0.78 mm criteria, 32,36,37,40 eight studies with CIMT ≥ 0.80 mm, 10,22,27,28,30,31,34,35 10 studies with CIMT ≥ 0.90 mm, 11,21,23–26,38,41,43 and four studies with CIMT ≥ 75th. 20,29,33,39…”

Cardiovascular disease risk in an urban African population: a cross-sectional analysis on the role of HIV and antiretroviral treatment

“…Results presented in the current analysis are in line with those from other, smaller, studies conducted in SSA. Gleason et al [49], Fourie et al [46] and Mosepele et al [18] all compared HIV-positive to HIV-negative participants in Ethiopia, South Africa and Botswana respectively, and observed no increase in CIMT based on HIV or ART status. Fourie et al [46], even found a lower CCA-IMT for the HIV-positive compared to the HIV-negative group.…”

“…The contribution made by ART to the development of CVD is a matter of debate. Although ART restores immune function, inflammatory markers do not return to normal levels, indicating ongoing low-grade inflammation, which is associated with CVD risk [16–18]. Older ART regimens evidently carry a high risk of metabolic side-effects, including lipodystrophy, altered glucose metabolism and dyslipidaemia, and have been associated with increased carotid intima-media thickness (CIMT), a marker of subclinical atherosclerosis [19].…”

Noncommunicable diseases in adolescents with perinatally acquired HIV-1 infection in high-income and low-income settings

“…Monocyte activation is associated with extensive pro-inflammatory biomarker expression (particularly IL-6, hsCRP, cystatin C) with consequent inflammatory endothelial damage that in turn allows circulating low-density lipoprotein (LDL) cholesterol particles entry into the intima where they become oxidized (oxLDL) [18**]. Monocyte activation, accompanied by elevated monocyte-specific markers (e.g., sCD14, sCD163, MCP-1), also promotes monocyte migration into the intima of large arteries where, in the presence of large amounts of oxLDL, they become dysfunctional foam cells [19].…”