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  • Open Access

High prevalence of the UGT1A1*28 variant in HIV-infected individuals in Greece

  • 1,
  • 2,
  • 2,
  • 2,
  • 3,
  • 3,
  • 3,
  • 3,
  • 3 and
  • 2
Journal of the International AIDS Society201013 (Suppl 4) :P146

https://doi.org/10.1186/1758-2652-13-S4-P146

  • Published:

Keywords

  • Bilirubin
  • Total Bilirubin
  • Type Locus
  • Common Adverse Event
  • Atazanavir

Background

Over the past few years there has been a remarkable increase in our knowledge of the variation in human genome. In parallel genotyping technologies have advanced significantly and allow sufficient throughput to accommodate genome-wide approaches. Hyperbilirubinemia is the most common adverse event in patients treated with atazanavir (ATV). Previous studies showed that polymorphisms in the uridine-glucuronosyl transferase (UGT1A1) enzyme and specifically the UGT1A1*28 variant may influence the risk of hyperbilirubinemia in patients treated with ATV/r.

Purpose of the study

Our objective was to estimate the prevalence of UGT1A1*28 polymorphism in HIV-infected individuals in Greece and to determine its potential association with hyperbilirubinemia in patients receiving boosted ATV (ATV/r).

Patients and methods

The prevalence of the UGTA1A1*28 variant was estimated in 80 HIV-infected patients retrospectively, (4/2009-5/2010) prior to the administration of the first-line treatment. Wilcoxon rank-sum test was used to determine whether the total bilirubin levels were different among carriers and non-carriers of the UGT1A1*28 polymorphism. The presence of the UGT1A1*28 allele was detected by PCR and DNA electrophoresis.

Results

The UGTA1A1*28 variant was detected in 45 out of 80 individuals (56.25%). Among 55 patients who received HAART, 20 received ATV/r as part of their first treatment. Of the ATV/r treated patients, 13 were found to be carriers of the UGT1A1*28 variant (65%). Total bilirubin levels were significantly higher in patients harbouring the UGT1A1*28 polymorphism (median value: 5.15 mg/dl) versus those harbouring the wild type UGT1A1 locus (median value mg/dl: 1.30) (p<0.01). The higher value of bilirubin was observed at week 4 of treatment whereas only 3 patients switched ATV/r to other Protease Inhibitor due to aesthetic problems. Hyperbilirubinemia (total bilirubin >1.3 mg/dl) was not detected in any patient with the UGT11A1*28 variant receiving any other therapy than ATV/r based first-line regimens.

Conclusions

Notably, 56% of the HIV-infected patients from a single HIV Unit in Greece carry at least one copy of the UGT1A1*28 allele. Carriers of the UGT1A1*28 variant treated with ATV/r based regimens had significantly higher levels of total bilirubin than those with UGT1A1 wild type locus, thus, suggesting the clinical utility of the UGT1A1 testing prior the administration of first-line treatment.

Authors’ Affiliations

(1)
Attikon University General Hospital, 4th Department of Internal Medicine, Athens, Greece
(2)
Medical School, University of Athens, Department of Hygiene, Epidemiology and Medical St, Athens, Greece
(3)
Attikon University General Hospital, 1st Rimini Street, Athens, Greece

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