Background: Greater T-cell activation was associated with reduced vascular compliance amongst persons living with HIV (PLWH) especially among overweight and obese individuals. There is a paucity of data regarding immune activation and arterial stiffness amongst PLWH in sub-Saharan Africa (SSA).Objective: To determine the association between immune activation and arterial stiffness in lean PLWH in SSA.Method: Forty-eight human immunodeficiency virus positive (HIV+) adults on antiretroviral therapy (ART) 5 years and 26 HIV-negative adults, all with BMI 25 kg/m2 and no history of CVD, were enrolled. The relationship of vascular compliance with circulating CD4+ and CD8+ naïve, memory, activated and senescent T cells, and serum 8-isoprostane was assessed by HIV status.Results: Increased immune activation was observed in the CD4+ and CD8+ T cells of PLWH, 16.7% vs. 8.9% and 22.0% vs. 12.4% respectively; p 0.001 (both). Furthermore, a higher proportion of senescent CD4+ T cells were associated with a lower carotid-femoral pulse wave velocity (cfPWV; p = 0.01), whilst a higher proportion of activated CD8+ T cells were associated with a lower carotid-radial pulse wave velocity (crPWV; p = 0.04), after adjustment for BMI and age. However, PLWH also had a higher median carotid-femoral augmentation index (cfAiX) (21.1% vs. 6.0%; p 0.05) in comparison to their HIV controls.Conclusion: Our population of lean PLWH had increased immune activation and higher cfAiX, a marker of arterial stiffness, compared to HIV-negative persons. The negative association between immune activation and arterial stiffness as measured by crPWV in PLHW on long-term treatment needs further elucidation.

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Background Impaired vascular compliance is common among persons with HIV (PWH) and a risk factor for cardiovascular disease (CVD), though many studies documenting this are from regions with a high prevalence of overweight and obesity. The prevalence and characteristics of impaired vascular compliance among PWH with low body mass index (BMI) is not well described, particularly in sub-Saharan Africa (SSA) where the majority of PWH live, a low BMI is more common, and the burden of CVD is rising. Aim To assess non-invasive vascular compliance measurements, including augmentation index (AIX), pulse wave velocity (PWV) and pulse waveforms, in underweight, normal weight, and overweight PWH on long-term antiretroviral therapy (ART) in SSA. Methods A cross-sectional study among PWH on ART at the University Teaching Hospital in Lusaka, Zambia. All participants had been on a regimen of efavirenz, emtricitabine, and tenofovir disoproxil fumarate for five or more years. Carotid-femoral PWV (cfPWV), carotid-radial PWV (crPWV), and the corresponding augmentation indexes (cfAIX and crAIX), were measured in all participants, in addition to aortic pressure waveforms, classified as type A, B, C and D according to reflected wave timings and amplitude. Multiple linear regression assessed relationships between demographic and clinical factors with vascular measurement endpoints. Results Ninety one PWH on long-term ART were enrolled; 38 (42%) were underweight (BMI < 18.5 kg/m2), 43 (47%) were normal weight (18.5–24.9 kg/m2) and 10 (11%) were overweight (> 25 kg/m2). Median age was 41, 40 and 40 years, among the three groups, respectively, and the proportion of women increased with BMI level. Overweight participants had a 39% higher cfAIX compared to normal-weight participants, while being underweight was associated with 27% lower cfAIX, after adjusting for age, sex and blood pressure (P = 0.02 and P = 0.01, respectively), but measurements of cfPWV, crPWV and crAIX did not differ. Conclusion Underweight PWH in SSA had lower cfAIX measurements compared to normal weight individuals, indicating less arterial stiffness. However, similar cfPWV, crPWV and crAIX values among the underweight and overweight PWH suggest a low BMI may not confer substantial protection against impaired vascular compliance as a contributor to CVD risk among individuals on ART.

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Background Endothelial function is dependent on the balance between vasoconstrictive and vasodilatory substances. The endothelium ability to produce nitric oxide is one of the most crucial mechanisms in regulating vascular tone. An increase in inducible nitric oxide synthase contributes to endothelial dysfunction in overweight persons, while oxidative stress contributes to the conversion of nitric oxide to peroxynitrite (measured as nitrotyrosine in vivo) in underweight persons. The objective of this study was to elucidate the interaction of body composition and oxidative stress on vascular function and peroxynitrite. This was done through an experimental design with three weight groups (underweight, normal weight and overweight), with four treatment arms in each. Plasma nitrotyrosine levels were measured 15–20 h post lipopolysaccharide (LPS) treatment, as were aortic ring tension changes. Acetylcholine (ACh) and sodium nitroprusside (SNP) challenges were used to observe endothelial-dependent and endothelial-independent vascular relaxation after pre-constriction of aortic rings with phenylephrine. Results Nitrotyrosine levels in saline-treated rats were similar among the weight groups. There was a significant increase in nitrotyrosine levels between saline-treated rats and those treated with the highest lipopolysaccharide doses in each of the weight groups. In response to ACh challenge, Rmax (percentage reduction in aortic tension) was lowest in overweight rats (112%). In response to SNP, there was an insignificantly lower Rmax in the underweight rats (106%) compared to the normal weight rats (112%). Overweight rats had a significant decrease in Rmax (83%) in response to SNP, signifying involvement of a more chronic process in tension reduction changes. A lower Rmax accompanied an increase in peroxynitrite after acetylcholine challenge in all weight groups. Conclusions Endothelial dysfunction, observed as an impairment in the ability to reduce tension, is associated with increased plasma peroxynitrite levels across the spectrum of body mass. In higher-BMI rats, an additional role is played by vascular smooth muscle in the causation of endothelial dysfunction.