Uridine metabolism in HIV-1-infected patients: effect of infection, of antiretroviral therapy and of HIV-1/ART-associated lypodystrophy syndrome

• Published in: PloS one 2010
• Main Authors: Domingo, Pere (Domingo Pedrol), Torres Torronteras, Javier, Pomar Solchaga, Virginia, Giralt i Oms, Marta, Domingo i Pedrol, Joan Carles, Gutiérrez, Maria del Mar, Gallego Escuredo, José Miguel, Mateo, Maria Gracia, Cano Soldado, Pedro Javier, Fernández, Irene, Pastor Anglada, Marçal, Vidal, Francesc, Villarroya i Gombau, Francesc, Andreu, Antoni, Martí, Ramon
• Format: Article
• Language: English
• Subjects: Antiretroviral agents; Antiretrovirals; HIV (Viruses); HIV-associated lipodystrophy syndrome; Metabolism; Metabolisme; Síndrome de lipodistròfia associada a VIH; VIH (Virus)
• ISSN: 1932-6203; 1932-6203

Background Uridine has been advocated for the treatment of HIV-1/HAART-associated lipodystrophy (HALS), although its metabolism in HIV-1-infected patients is poorly understood. Methods Plasma uridine concentrations were measured in 35 controls and 221 HIV-1-infected patients and fat uridine in 15 controls and 19 patients. The diagnosis of HALS was performed following the criteria of the Lipodystrophy Severity Grading Scale. Uridine was measured by a binary gradient-elution HPLC method. Analysis of genes encoding uridine metabolizing enzymes in fat was performed with TaqMan RT-PCR. Results Median plasma uridine concentrations for HIV-1-infected patients were 3.80 µmol/l (interquartile range: 1.60), and for controls 4.60 µmol/l (IQR: 1.8) (P = 0.0009). In fat, they were of 6.0 (3.67), and 2.8 (4.65) nmol/mg of protein, respectively (P = 0.0118). Patients with a mixed HALS form had a median plasma uridine level of 4.0 (IC95%: 3.40-4.80) whereas in those with isolated lipoatrophy it was 3.25 (2.55-4.15) µmol/l/l (P = 0.0066). The expression of uridine cytidine kinase and uridine phosphorylase genes was significantly decreased in all groups of patients with respect to controls. A higher expression of the mRNAs for concentrative nucleoside transporters was found in HIV-1-infected patients with respect to healthy controls. Conclusions HIV-1 infection is associated with a decrease in plasma uridine and a shift of uridine to the adipose tissue compartment. Antiretroviral therapy was not associated with plasma uridine concentrations, but pure lipoatrophic HALS was associated with significantly lower plasma uridine concentrations.