Low levels of short- and medium-chain acylcarnitines in HIV-infected patients

• Published in: European journal of clinical investigation 2016-05, Vol.46 (5), p.408-417
• Main Authors: Waagsbø, Bjørn, Svardal, Asbjørn, Ueland, Thor, Landrø, Linn, Øktedalen, Olav, Berge, Rolf K., Flo, Trude H., Aukrust, Pål, Damås, Jan K.
• Format: Article
• Language: English
• Subjects: Adult; Antiretroviral Therapy, Highly Active; Carnitine - analogs & derivatives; Carnitine - blood; Carnitine ester profile; Case-Control Studies; Disease Progression; Female; HIV; HIV Infections - blood; HIV Infections - complications; HIV Infections - drug therapy; Humans; Interferon-gamma; Interferon-gamma Release Tests; Longitudinal Studies; Male; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection - blood; Mycobacterium avium-intracellulare Infection - complications; Tumor Necrosis Factor-alpha
• ISSN: 0014-2972; 1365-2362
• DOI: 10.1111/eci.12609

Background Carnitine plays an essential role in fatty acid metabolism, exerts substantial antioxidant action and regulates immune functions. We hypothesized that a disturbed carnitine metabolism could be involved in progression of HIV infection. Materials and methods Plasma levels of L‐carnitine, its precursors, and short‐, medium‐ and long‐chain acylcarnitines were analysed with HPLC/mass spectrometry in HIV‐infected patients with various disease severities including patients who acquired Mycobacterium avium complex (MAC) infection. In vitro, we examined the MAC‐purified protein derivate (PPD)‐induced release of TNF‐α and IFN‐γ in peripheral blood mononuclear cells (PBMCs) from patients with either high or low plasma levels of acylcarnitines. Results Plasma levels of the short‐chain (e.g. propionyl‐carnitine) and medium‐chain (e.g. octanoyl‐carnitine) acylcarnitines were reduced in patients with advanced HIV infection. These acylcarnitines gradually decreased in rapid progressors, while minimal changes were observed in the nonprogressors. Plasma levels of propionyl‐carnitine and octanoyl‐carnitine significantly increased during antiretroviral therapy (ART). However, ART did not restore levels to those observed in healthy controls. Depletion of propionyl‐carnitine and octanoyl‐carnitine was observed prior to MAC infection, and the release of TNF‐α and IFN‐γ from PBMC was decreased after stimulation with MAC‐PPD in samples from HIV‐infected patients with low levels of propionyl‐carnitine or octanoyl‐carnitine. Conclusions Our findings suggest an association between disturbed acylcarnitine metabolism, immune dysregulation and disease progression in HIV‐infected patients. Low levels of propionyl‐carnitine and octanoyl‐carnitine were associated with increased susceptibility to MAC infection in HIV patients with advanced disease.