Asymmetric Dimethylarginine Concentrations Decrease in Patients with HIV Infection under Antiretroviral Therapy

Abstract

In HIV-infected patients, elevated plasma concentrations of the endogenous nitric oxide synthase inhibitor and cardiovascular risk factor asymmetric dimethylarginine (ADMA) are documented, and levels correlate with markers of immune activation, such as neopterin. In this study, the effect of antiretroviral therapy (ART) on arginine, ADMA and symmetric dimethylarginine (SDMA) levels was investigated and related to changes of immune activation markers and lipids. Concentrations of ADMA, SDMA, arginine, C-reactive protein (CRP) and neopterin were determined in 112 HIV-infected patients after 12 months of successful ART, as reflected by undetectable HIV RNA levels, and compared to baseline levels. ADMA, SDMA, arginine and urine neopterin levels were determined by HPLC, and plasma neopterin concentrations by ELISA. Disease activity before and after treatment was monitored by determination of HIV RNA levels and CD4(+) T-cell counts. Lipids and CRP were determined by routine laboratory assays. Under treatment with ART, concentrations of ADMA, SDMA and arginine dropped in parallel with decreasing HIV RNA levels and neopterin concentrations, while cholesterol, triglyceride levels and CD4(+) T-cell counts increased. CRP levels did not change. After ART, a significant inverse association between ADMA and plasma cholesterol was observed. Successful ART, defined by HIV RNA levels below the limit of detection, leads to decreasing levels of methylated arginines and immune activation markers. Thus, it is unlikely that disturbances of dimethylarginine metabolism account for the increased risk of cardiovascular events of HIV-infected patients under ART.