The cardiovascular risk marker asymmetric dimethylarginine is elevated in asymptomatic, untreated HIV-1 infection and correlates with markers of immune activation and disease progression

Abstract

Background: As lifespan in HIV infection increases, cardiovascular disease has emerged as a cause of morbidity and mortality. Asymmetric dimethylarginine is an established marker of endothelial dysfunction and predicts cardiovascular events. The role of asymmetric dimethylarginine in HIV-related cardiovascular disease has not been established. Our aim was to determine whether asymmetric dimethylarginine concentrations were elevated in treatment naïve, HIV-infected subjects and to correlate these with markers of immune activation and disease progression. Methods: Serum samples were collected from HIV-positive and -negative subjects attending a primary health care clinic over a 12-month period. Asymmetric dimethylarginine concentrations were measured and correlated with CD4 count, viral load, hsCRP, IL-6, IgG, adenosine deaminase and CD8/38 T lymphocytes. Results: Sixty HIV-positive participants (mean age 32.0 years) and 20 HIV-negative controls (mean age 32.4 years) were studied. All were of black ethnicity. The mean asymmetric dimethylarginine concentration in the infected group measured 0.67 mmol/L (95% CI 0.62-0.72 mmol/L) which was significantly higher than in the control group of 0.48 mmol/L (95% CI 0.40-0.56 mmol/L). Asymmetric dimethylarginine correlated inversely with CD4 counts and positively with IgG, adenosine deaminase and CD8/38 T lymphocytes. No significant correlation was found with hsCRP, IL-6, or viral load. Conclusion: We demonstrated that asymmetric dimethylarginine is elevated in HIV infection, in patients with relatively well-preserved CD4 counts not yet on anti-retroviral treatment. We showed significant correlations of asymmetric dimethylarginine with CD8/38 T lymphocytes, IgG and adenosine deaminase, suggesting that T-cell activation and the adaptive immune response underlie asymmetric dimethylarginine elevation in this population.

Comprehensive assessment of the arginine pathway and its relationship to inflammation in HIV

“…Contrary to our findings, ADMA has been found to be higher in HIV-infected subjects versus controls in separate reports [10, 19]. The difference in mean ADMA reported between HIV-infected and HIV uninfected individuals has ranged between 0.03 μmol/L–0.18 μmol/L [10, 19, 20].…”

“…Contrary to our findings, ADMA has been found to be higher in HIV-infected subjects versus controls in separate reports [10, 19]. The difference in mean ADMA reported between HIV-infected and HIV uninfected individuals has ranged between 0.03 μmol/L–0.18 μmol/L [10, 19, 20]. Mean levels of ADMA in HIV-infected individuals in our study was similar to what was found in previous reports of HIV-infected individuals who were ART-naïve and were younger than our patients [11, 19], however, levels in HIV-uninfected individuals were 0.18 umol/L higher in our study than what has been reported [19, 4].…”

“…The difference in mean ADMA reported between HIV-infected and HIV uninfected individuals has ranged between 0.03 μmol/L–0.18 μmol/L [10, 19, 20]. Mean levels of ADMA in HIV-infected individuals in our study was similar to what was found in previous reports of HIV-infected individuals who were ART-naïve and were younger than our patients [11, 19], however, levels in HIV-uninfected individuals were 0.18 umol/L higher in our study than what has been reported [19, 4]. We hypothesize that our findings could be the result of several factors inherent to the demographics of our participants.…”

Neuropathogenesis of HIV: From Initial Neuroinvasion to HIV-Associated Neurocognitive Disorder (HAND)

“…For example, ADMA, a biomarker of endothelial dysfunction, is increased in patients with asymptomatic HIV infection (79), and could be posited associate with disruption of the blood brain barrier and HAND. While the role of ADMA remains unknown, this is one of a group of novel biomarkers which need to be explored to optimize assessment of HIV and guide HIV care, particularly in patients at risk for HAND.…”