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

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 µmol/L (95% CI 0.62-0.72 µmol/L) which was significantly higher than in the control group of 0.48 µmol/L (95% CI 0.40-0.56 µmol/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.