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

Dirajlal-Fargo, Sahera; Alam, Khurshid; Sattar, Abdus; Kulkarni, Manjusha; Funderburg, Nicholas; Wilson, Wai Hong; McComsey, Grace A.

doi: 10.1097/QAD.0000000000001363
Clinical Science: Concise Communications

Background: Nitric oxide helps maintain vascular function and is generated through the oxidation of arginine. Whether altered arginine metabolism may lead to elevated levels of inflammation in HIV is unclear.

Methods: We performed a cross-sectional analysis of HIV-infected adults on stable antiretroviral therapy with HIV-1 RNA less than 50 copies/ml and HIV-uninfected controls. We measured biomarkers in the arginine pathway, markers of systemic inflammation, and monocyte activation. T-tests, χ2 tests, and propensity score matching analyses were used to compare markers by HIV status, and multiple linear regressions were used to assess associations of arginine metabolites with markers of inflammation.

Results: Overall, 131 participants were enrolled (93 HIV-infected and 38 HIV-uninfected controls); 70% were men; 58% African-Americans; median age was 51 years, median absolute CD4+ was 735 cell/mm3. Lysine, arginine, citrulline, global arginine bioavailability ratio, and symmetrical dimethylarginine were different between HIV-infected and HIV-uninfected adults (P = ≤0.02), but asymmetric dimethylarginine was not (P ≥ 0.13). Arginine biomarkers in HIV-infected, but not in HIV-uninfected controls, were associated with all measured markers of inflammation, endothelial activation, and coagulation (P ≤ 0.05).

Conclusion: HIV-infected participants on antiretroviral therapy with virologic suppression have altered plasma levels of biomarkers in the arginine pathway compared with controls. These biomarkers are independently associated with markers of inflammation and monocyte activation in HIV.

aCase Western Reserve University

bRainbow Babies and Children's Hospital, Cleveland

cOhio State University, Columbus

dCleveland Clinic, Cleveland, Ohio, USA.

Correspondence to Grace A. McComsey, MD, FIDSA, Professor of Pediatrics and Medicine Chief, Division of Pediatric Infectious Diseases and Rheumatology, Case School of Medicine, 2061 Cornell Rd- Mail Stop: 5083, Cleveland, OH 44106, USA. E-mail:

Received 15 September, 2016

Revised 14 November, 2016

Accepted 27 November, 2016

Copyright © 2017 Wolters Kluwer Health, Inc.