Immune activation and arterial stiffness in lean adults with HIV on antiretroviral therapy

Abstract

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.

Aortic Pressure Levels and Waveform Indexes in People Living With Human Immunodeficiency Virus: Impact of Calibration Method on the Differences With Respect to Non-HIV Subjects and Optimal Values

“…These observations stressed out the relevance of reaching a consensus and systematization on the methodology used for the non-invasive assessment of central hemodynamics, since otherwise “different results” can be obtained despite analyzing the same patient. Consequently, it is not surprising, that controversial results have been reported on central hemodynamics between subjects with and without HIV infection ( 9 – 15 ). However, some considerations need to be pointed out.…”

“…At least three factors could explain these controversies. First, prior studies that have reported aoBP levels and waveform-derived indexes in PLWHIV compared to HIV- subjects either (i) did not adjust for any CRF ( 9 , 15 ) or (ii) only adjusted for some variables (e.g., age, sex, body mass index) without considering other cofactors such as cholesterol, triglycerides and diabetes ( 10 – 14 ). Thus, it remains to be determined at what extent potential differences in central hemodynamics associated with HIV infection would be directly related to the disease condition and/or would be determined by the presence of concomitant CRFs.…”

“…Thus, it remains to be determined at what extent potential differences in central hemodynamics associated with HIV infection would be directly related to the disease condition and/or would be determined by the presence of concomitant CRFs. Second, certain studies have considered control groups (HIV-) with relatively small sample size (e.g., n = 26–37) ( 9 , 10 , 15 ), which significantly reduces the statistical power of the tests to find significant differences between the groups (Type-II error). Last, these studies have not considered the relevance of the calibration of the pressure waveform at the time of assessing non-invasively central hemodynamics ( 16 ).…”

“…Last, these studies have not considered the relevance of the calibration of the pressure waveform at the time of assessing non-invasively central hemodynamics ( 16 ). Several studies that have compared the aoBP between PLWHIV and HIV- subjects either did not report the calibration method ( 9 , 10 , 13 , 15 ) or used currently not recommended schemes (i.e., systolic-diastolic calibration; see below) ( 11 , 14 ).…”

Vascular dysfunction and body mass index in African adults with HIV

“…Most studies using non-invasive physiological measures of vascular function have reported impaired vascular compliance in overweight/obese PWH who are already at risk of CVD [10,23]. Our group previously reported that lean PWH on ART for more than five years had increased arterial stiffness using the measure AIX [24]. However, reports of PWV measurements in PWH, especially lean individuals, have been inconsistent.…”