Relationship of Body Composition, Metabolic Status, Antiretroviral Use, and HIV Disease Factors to Endothelial Dysfunction in HIV-Infected Subjects

Abstract

Vascular endothelial dysfunction may contribute to the increase in cardiovascular events during HIV-1 infection and its treatment. Antiretroviral therapy (ART), metabolic factors, lipodystrophy, and HIV infection itself may be involved. Ninety-six HIV-infected subjects were evaluated for endothelial function by measurement of brachial artery flow-mediated dilation (FMD) by ultrasound, single-slice CT of the abdomen and mid-thigh, wholebody dual x-ray absorptiomety (DXA) scans, and metabolic evaluations in a cross-sectional study. The median age was 40 years; 28% were female, 38% black, 3% Hispanic, and 59% white. Forty-nine (51%) were receiving ART, which included a PI in 28 (57%) and was non-PI based in 21 (43%). FMD (AESD) in subjects not on ART was 5.5 AE 4.3%, PI-ART 5.3 AE 3.6%, and non-PI-ART 5.5 AE 4.1% ( p ¼ 0.9). Age, race, CD4 cell count, and HIV RNA did not correlate significantly with FMD. Among ART-treated subjects in the lowest tertile of thigh subcutaneous fat area (range 3-31 cm 2 ), FMD was 4.4 AE 3.5% and in the highest tertile (range 67-237 cm 2 ) FMD was 6.8 AE 3.6% ( p ¼ 0.07, t-test). However, in multivariate analyses, no body composition measure showed a significant association with FMD for either the group as a whole or in ART-treated subjects. ART use, PI use, CD4 cell count, and HIV RNA levels were not associated with endothelial dysfunction by brachial FMD. A definitive association with measures of adiposity was not detected in multivariate analysis, suggesting that lipoatrophy may not be an important contributor to endothelial dysfunction in HIV-infected individuals on ART.

Microbial Translocation and Metabolic and Body Composition Measures in Treated and Untreated HIV Infection

“…20 This cohort represented two distinct groups: (1) stable subjects not receiving ART, with relatively well-maintained CD4 cell counts, and (2) subjects receiving prolonged ongoing ART, with 84% undetectable HIV RNA.…”

“…Lipids, lipoproteins by nuclear magnetic resonance (NMR), glucose, insulin, and inflammatory markers were measured as originally described. 18,20 In both studies, insulin sensitivity was estimated by homeostasis model assessment-insulin resistance (HOMA-IR). 21 …”

“…20,22 DXA scans were done at baseline and week 48 in ACTG 5142. 22 Additionally, in the IU study, a single-slice computed tomography (CT) of the abdomen at L4-5 was performed to estimate visceral and subcutaneous fat.…”

Mitochondrial DNA Variation and Changes in Adiponectin and Endothelial Function in HIV-Infected Adults After Antiretroviral Therapy Initiation

“…Nucleoside reverse transcriptase inhibitors (NRTIs) are associated with mitochondrial and metabolic toxicities, 5,6 including endothelial dysfunction in some studies, 7,8 but not in others. 9 Mitochondrial DNA (mtDNA) encodes electron transport chain subunits that are critical for energy production, and mitochondrial function influences vascular health. 10 Combinations of single nucleotide polymorphisms (SNPs) within mtDNA allow for categorization of individuals into haplogroups.…”

Adipokines and vascular health in treated HIV infection

“…The Study of Fat Redistribution and Metabolic Change in HIV infection did not report associations of IMT with measures of adiposity [19]; however, in separate analyses, higher subcutaneous adipose tissue (SAT) was associated with higher leptin, paradoxically higher adiponectin [2], and lower Framingham risk [20]. In a study of endothelial function that included a small number of women ( n = 27), both SAT and leptin concentration were positively correlated with FMD, although the relationship was attenuated in multivariable models [21]. Finally, we have previously described a positive correlation between BMI and FMD independent of other risk factors in a majority male population [22].…”