HIV-positive youth who are perinatally infected have impaired endothelial function

Abstract

Objective-Evaluating cardiovascular (CVD) risk in children and youth 13-24 years old who are facing a lifetime exposure to both HIV and antiretroviral therapy (ART) is a research priority. This study compares endothelial function measured by Peripheral Arterial Tonometry in HIV+ youth infected perinatally and behaviorally as well as HIV-controls.Methods-Three groups of participants aged 8-30 yo were enrolled; HIV+ perinatally-infected, HIV+ behaviorally-infected on ART with HIV-1 RNA <1,000 copies/mL, and HIV-controls. We measured the reactive hyperemic index (RHI), a measure of endothelial function, using endoPAT. Markers of systemic inflammation, monocyte activation, and gut integrity were also assessed. Spearman correlations and regression analyses were used to explore relationships between endothelial function measures and other measured variables.Results-Overall, 119 participants were enrolled: 53 HIV +behaviorally infected, 18 HIV+ perinatally-infected, and 48 controls. Overall, 71 % were men; 77% African Americans and median age was 22 years old. Median (interquartile range) RHI was lower in the HIV+ perinatallyinfected group [1.34 (1.20, 1.42)], compared to the behaviorally infected group [1.52 (1.34, 1.75)] and the control group [1.52 (1.27, 1.80) (p<0.01)]. Soluble CD14, a marker of monocyte activation, intestinal fatty acid-binding protein, a marker of gut integrity and soluble vascular cell adhesion molecule, a marker of vascular dysfunction, were different among the 3 groups (p≤0.01). Author Contributions: SDF and GAM designed the study, SDF and GAM obtained funding. AS provided statistical support, MK and NF assisted with the inflammation and immune activation marker assays. SDF wrote the first draft of the manuscript. All authors contributed to data analysis and reviewed the manuscript for intellectual content.Conflicts of Interest: GAM served as a consultant for Gilead, BMS, GSK/Viiv, and ICON, and has received research funding from Gilead, Merck, GSK/Viiv, and BMS. NF served as a consultant for Gilead. HHS Public Access Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptConclusions-HIV+ youth infected perinatally appear to have higher levels of endothelial dysfunction and immune activation when compared to behaviorally-infected youth. Further longitudinal studies are needed to determine whether perinatally-infected youth have higher risks of CVD.

Insulin Resistance in South African Youth Living with Perinatally Acquired HIV Receiving Antiretroviral Therapy

“…31 In YLPHIV, a higher prevalence of risk factors for subclinical vascular disease, including a higher Pathobiological Determinants of Atherosclerosis (PDAY) score, has been documented. [32][33][34] In YLPHIV with a high PDAY score, a switch from an abacavir-containing regimen score may be warranted.…”

Cardiac and inflammatory biomarkers in perinatally HIV-infected and HIV-exposed uninfected children

“…A recent report emphasized that longitudinal studies evaluating cardiovascular risk in PHIV children are “crucial” and a “research priority”. 53 The role of cardiac and inflammatory biomarkers in cardiovascular risk assessment needs to be studied longitudinally to determine their value in cardiovascular risk stratification for PHIV youth.…”

Vascular endothelial dysfunction in the wake of HIV and ART

“…Similarly, both HIV-1 infection and its treatment have been linked to endothelial dysfunction, with oxidative stress branded the apparent culprit [19]. Dirajlal-Fargo et al [20] found perinatally infected HIV-positive youth to have higher levels of endothelial dysfunction and immune activation when compared to their behaviourally infected counterparts, possibly due to a longer cumulative duration of HIV infection. These researchers indicate that multiple factors, including metabolic factors, inflammation and ART regimen, contribute to the progression of vascular disease in HIV-infected youth.…”