Abstract
BackgroundCirculating levels of microbial products are increased in HIV infection, and provoke endothelial dysfunction in other disease settings.Methodology/Principal FindingsWe examined data from a cross-sectional single site study at Indiana University (Indiana, N = 85) and a 24- week multicenter prospective study of antiretroviral therapy (ART) initiation (ACTG 5152s, N = 75). Brachial artery flow-mediated dilation (FMD) was measured by ultrasound. Plasma lipopolysaccharide (LPS) and soluble CD14 (sCD14) levels were measured from stored specimens and correlated with FMD values using Pearson correlations. The Indiana subjects were 63% male with a mean age of 39 years and a median CD4 count of 406 cells/mm3 (388 not on ART, 464 on ART). The 5152s subjects were 92% were male with a mean age of 35 years and a median CD4 count of 251 cells/mm3 at entry which increased to 396 cells/mm3 on ART. When analyzing the two cohorts individually or in combination neither sCD14 nor LPS correlated significantly with FMD. In a pre-specified subgroup analysis of the Indiana subjects receiving ART (N = 46, mean ART duration 40 months) LPS was inversely correlated with FMD (r = −0.33, p = 0.02), but not sCD14 (r = −0.01, p = 0.9). Multivariate analysis confirmed LPS as an independent predictor of FMD in this subgroup (p = 0.02).Conclusions/Significance In HIV- infected individuals on prolonged ART, higher LPS levels are associated with worse endothelial function but not in untreated subjects or at 24 weeks after ART initiation. Persistent microbial translocation may contribute to arterial dysfunction and the increased cardiovascular disease risk observed in individuals on long-term ART.
Highlights
HIV infection has been associated with increased cardiovascular disease risk [1] but the mediators of the increased risk have not been identified
Factors other than protease inhibitors (PIs) use that may contribute to endothelial dysfunction in HIV-infected patients include untreated HIV infection itself [5] treatment-associated lipid changes [4,6] and the lipodystrophy syndrome [7].Mediators and markers of endothelial dysfunction have been sought, such as lipids and lipoproteins and circulating markers of inflammation and vascular activation, but the majority of these factors have not been significantly associated with endothelial function as measured by brachial flow-mediated dilation (FMD) [5,8]
Our aim was to establish a relationship between microbial translocation measures and endothelial dysfunction in HIVinfected subjects in two well-characterized study populations [5,8] which used FMD as a marker of endothelial function
Summary
HIV infection has been associated with increased cardiovascular disease risk [1] but the mediators of the increased risk have not been identified. Long-term use of protease inhibitors (PIs) has been associated with endothelial dysfunction [4]. Lack of a consistent association between FMD and CD4 cell count suggests that immune status is not directly related to endothelial dysfunction [5,8,9,10,11]. In a large cohort study, there was no association between CD4 cell count and risk of myocardial infarction [12]. The specific mediators of HIV-associated endothelial dysfunction have not been identified. Circulating levels of microbial products are increased in HIV infection, and provoke endothelial dysfunction in other disease settings
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
