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: Pere Domingo, Javier Torres-Torronteras, Virginia Pomar, Marta Giralt, Joan Carles Domingo, Maria Del Mar Gutierrez, José M Gallego-Escuredo, Maria Gracia Mateo, Pedro Cano-Soldado, Irene Fernandez, Marçal Pastor-Anglada, Francesc Vidal, Francesc Villarroya, Antoni Andreu, Ramon Marti
• Journal: PloS one (PLoS One) Vol. 5 Issue 11 Pg. e13896 (Nov 15 2010) ISSN: 1932-6203 [Electronic] United States
• PMID: 21085568 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Lipids
• Nucleoside Transport Proteins
• Uridine Phosphorylase
• Uridine Kinase
• Uridine

Topics

• Adipose Tissue (drug effects, metabolism)
• Adult
• Antiretroviral Therapy, Highly Active
• Female
• Gene Expression
• HIV Infections (drug therapy, genetics, metabolism)
• HIV-1 (drug effects)
• HIV-Associated Lipodystrophy Syndrome (chemically induced, diagnosis, metabolism)
• Humans
• Lipids (analysis)
• Male
• Middle Aged
• Nucleoside Transport Proteins (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Uridine (blood, metabolism)
• Uridine Kinase (genetics, metabolism)
• Uridine Phosphorylase (genetics, metabolism)