title: Uridine metabolism in HIV-1-infected patients: effect of infection, of antiretroviral therapy and of HIV-1/ART-associated lipodystrophy syndrome.
abstract: 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.
authors.affiliation: Infectious Diseases Unit, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain. pdomingo@santpau.cat
authors.forename: Pere
authors.initials: P
authors.lastname: Domingo
authors.forename: Javier
authors.initials: J
authors.lastname: Torres-Torronteras
authors.forename: Virginia
authors.initials: V
authors.lastname: Pomar
authors.forename: Marta
authors.initials: M
authors.lastname: Giralt
authors.forename: Joan Carles
authors.initials: JC
authors.lastname: Domingo
authors.forename: Maria Del Mar
authors.initials: Mdel M
authors.lastname: Gutierrez
authors.forename: José M
authors.initials: JM
authors.lastname: Gallego-Escuredo
authors.forename: Maria Gracia
authors.initials: MG
authors.lastname: Mateo
authors.forename: Pedro
authors.initials: P
authors.lastname: Cano-Soldado
authors.forename: Irene
authors.initials: I
authors.lastname: Fernandez
authors.forename: Marçal
authors.initials: M
authors.lastname: Pastor-Anglada
authors.forename: Francesc
authors.initials: F
authors.lastname: Vidal
authors.forename: Francesc
authors.initials: F
authors.lastname: Villarroya
authors.forename: Antoni
authors.initials: A
authors.lastname: Andreu
authors.forename: Ramon
authors.initials: R
authors.lastname: Marti
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D005260:Female; D015870:Gene Expression; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects*; D039682:HIV-Associated Lipodystrophy Syndrome / Q000139:chemically induced / Q000175:diagnosis / Q000378:metabolism; D006801:Humans; D008055:Lipids / Q000032:analysis; D008297:Male; D008875:Middle Aged; D033703:Nucleoside Transport Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014529:Uridine / Q000097:blood / Q000378:metabolism*; D014541:Uridine Kinase / Q000235:genetics / Q000378:metabolism; D014543:Uridine Phosphorylase / Q000235:genetics / Q000378:metabolism
chemical_list: D008055:Lipids; D033703:Nucleoside Transport Proteins; D014543:Uridine Phosphorylase; D014541:Uridine Kinase; D014529:Uridine