Switching to unboosted atazanavir reduces bilirubin and triglycerides without compromising treatment efficacy in UGT1a1*28 polymorphism carriers

Laurenzia Ferraris, Ottavia Viganö, Anna Peri, Maciej Tarkowski, Greta Milani, Stefano Bonora, Fulvio Adorni, Cristina Gervasoni, Emilio Clementi, Giovanni Di perri, Massimo Galli, Agostino Riva

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Objectives: Hyperbilirubinaemia is a frequent complication of atazanavir-containing antiretroviral therapy and its severity is related to UDP-glucuronosyl transferase (UGT) 1A1*28 polymorphism. The aim of this study was to evaluate the safety and outcome of unboosted atazanavir-containing regimens based on the genetic constitution. Methods: Fifty-one HIV-1-infected patients on boosted atazanavir were prospectively enrolled in the study. Twenty-five patients with a UGT1A1*28 allele switched to 400 mg of unboosted atazanavir. Results: At baseline, UGT1A1 heterozygous and homozygous patients had significantly higher bilirubin levels than wild-type (P = 0.012 and P <0.001, respectively). After ritonavir removal, a reduction was observed in total bilirubin (from 4.09 to 1.82 mg/dL; P <0.001), γ-glutamyl transpeptidase (P = 0.015), triglycerides (P = 0.03) and total cholesterol (P = 0.05). No significant changes in CD4 T cell count and no increases in viral load were observed 12 months after unboosting. Plasma drug monitoring after ritonavir removal revealed the presence of therapeutic atazanavir concentrations in all patients except one with poor therapy adherence. Conclusions: UGT1A1*28 is significantly related to hyperbilirubinaemia in HIV-1 patients receiving atazanavir. Genotyping before the initiation of antiretroviral therapy can reduce the emergence of severe hyperbilirubinaemia. Unboosted atazanavir-containing therapy is safe and efficacious in patients with an undetectable viral load with a UGT1A1*28 polymorphism, allowing the use of atazanavir in patients otherwise likely unable to receive it.

Original languageEnglish
Article numberdks175
Pages (from-to)2236-2242
Number of pages7
JournalJournal of Antimicrobial Chemotherapy
Volume67
Issue number9
DOIs
Publication statusPublished - Sep 2012

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Bilirubin
Triglycerides
Hyperbilirubinemia
Ritonavir
Viral Load
HIV-1
Therapeutics
Uridine Diphosphate
gamma-Glutamyltransferase
Atazanavir Sulfate
Drug Monitoring
Constitution and Bylaws
CD4 Lymphocyte Count
Transferases
Alleles
Cholesterol
T-Lymphocytes
Safety

Keywords

  • Antiretroviral therapy
  • HIV
  • Hyperbilirubinaemia
  • Pharmacogenetics
  • Therapeutic drug monitoring

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Switching to unboosted atazanavir reduces bilirubin and triglycerides without compromising treatment efficacy in UGT1a1*28 polymorphism carriers. / Ferraris, Laurenzia; Viganö, Ottavia; Peri, Anna; Tarkowski, Maciej; Milani, Greta; Bonora, Stefano; Adorni, Fulvio; Gervasoni, Cristina; Clementi, Emilio; Di perri, Giovanni; Galli, Massimo; Riva, Agostino.

In: Journal of Antimicrobial Chemotherapy, Vol. 67, No. 9, dks175, 09.2012, p. 2236-2242.

Research output: Contribution to journalArticle

Ferraris, L, Viganö, O, Peri, A, Tarkowski, M, Milani, G, Bonora, S, Adorni, F, Gervasoni, C, Clementi, E, Di perri, G, Galli, M & Riva, A 2012, 'Switching to unboosted atazanavir reduces bilirubin and triglycerides without compromising treatment efficacy in UGT1a1*28 polymorphism carriers', Journal of Antimicrobial Chemotherapy, vol. 67, no. 9, dks175, pp. 2236-2242. https://doi.org/10.1093/jac/dks175
Ferraris, Laurenzia ; Viganö, Ottavia ; Peri, Anna ; Tarkowski, Maciej ; Milani, Greta ; Bonora, Stefano ; Adorni, Fulvio ; Gervasoni, Cristina ; Clementi, Emilio ; Di perri, Giovanni ; Galli, Massimo ; Riva, Agostino. / Switching to unboosted atazanavir reduces bilirubin and triglycerides without compromising treatment efficacy in UGT1a1*28 polymorphism carriers. In: Journal of Antimicrobial Chemotherapy. 2012 ; Vol. 67, No. 9. pp. 2236-2242.
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abstract = "Objectives: Hyperbilirubinaemia is a frequent complication of atazanavir-containing antiretroviral therapy and its severity is related to UDP-glucuronosyl transferase (UGT) 1A1*28 polymorphism. The aim of this study was to evaluate the safety and outcome of unboosted atazanavir-containing regimens based on the genetic constitution. Methods: Fifty-one HIV-1-infected patients on boosted atazanavir were prospectively enrolled in the study. Twenty-five patients with a UGT1A1*28 allele switched to 400 mg of unboosted atazanavir. Results: At baseline, UGT1A1 heterozygous and homozygous patients had significantly higher bilirubin levels than wild-type (P = 0.012 and P <0.001, respectively). After ritonavir removal, a reduction was observed in total bilirubin (from 4.09 to 1.82 mg/dL; P <0.001), γ-glutamyl transpeptidase (P = 0.015), triglycerides (P = 0.03) and total cholesterol (P = 0.05). No significant changes in CD4 T cell count and no increases in viral load were observed 12 months after unboosting. Plasma drug monitoring after ritonavir removal revealed the presence of therapeutic atazanavir concentrations in all patients except one with poor therapy adherence. Conclusions: UGT1A1*28 is significantly related to hyperbilirubinaemia in HIV-1 patients receiving atazanavir. Genotyping before the initiation of antiretroviral therapy can reduce the emergence of severe hyperbilirubinaemia. Unboosted atazanavir-containing therapy is safe and efficacious in patients with an undetectable viral load with a UGT1A1*28 polymorphism, allowing the use of atazanavir in patients otherwise likely unable to receive it.",
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AU - Ferraris, Laurenzia

AU - Viganö, Ottavia

AU - Peri, Anna

AU - Tarkowski, Maciej

AU - Milani, Greta

AU - Bonora, Stefano

AU - Adorni, Fulvio

AU - Gervasoni, Cristina

AU - Clementi, Emilio

AU - Di perri, Giovanni

AU - Galli, Massimo

AU - Riva, Agostino

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N2 - Objectives: Hyperbilirubinaemia is a frequent complication of atazanavir-containing antiretroviral therapy and its severity is related to UDP-glucuronosyl transferase (UGT) 1A1*28 polymorphism. The aim of this study was to evaluate the safety and outcome of unboosted atazanavir-containing regimens based on the genetic constitution. Methods: Fifty-one HIV-1-infected patients on boosted atazanavir were prospectively enrolled in the study. Twenty-five patients with a UGT1A1*28 allele switched to 400 mg of unboosted atazanavir. Results: At baseline, UGT1A1 heterozygous and homozygous patients had significantly higher bilirubin levels than wild-type (P = 0.012 and P <0.001, respectively). After ritonavir removal, a reduction was observed in total bilirubin (from 4.09 to 1.82 mg/dL; P <0.001), γ-glutamyl transpeptidase (P = 0.015), triglycerides (P = 0.03) and total cholesterol (P = 0.05). No significant changes in CD4 T cell count and no increases in viral load were observed 12 months after unboosting. Plasma drug monitoring after ritonavir removal revealed the presence of therapeutic atazanavir concentrations in all patients except one with poor therapy adherence. Conclusions: UGT1A1*28 is significantly related to hyperbilirubinaemia in HIV-1 patients receiving atazanavir. Genotyping before the initiation of antiretroviral therapy can reduce the emergence of severe hyperbilirubinaemia. Unboosted atazanavir-containing therapy is safe and efficacious in patients with an undetectable viral load with a UGT1A1*28 polymorphism, allowing the use of atazanavir in patients otherwise likely unable to receive it.

AB - Objectives: Hyperbilirubinaemia is a frequent complication of atazanavir-containing antiretroviral therapy and its severity is related to UDP-glucuronosyl transferase (UGT) 1A1*28 polymorphism. The aim of this study was to evaluate the safety and outcome of unboosted atazanavir-containing regimens based on the genetic constitution. Methods: Fifty-one HIV-1-infected patients on boosted atazanavir were prospectively enrolled in the study. Twenty-five patients with a UGT1A1*28 allele switched to 400 mg of unboosted atazanavir. Results: At baseline, UGT1A1 heterozygous and homozygous patients had significantly higher bilirubin levels than wild-type (P = 0.012 and P <0.001, respectively). After ritonavir removal, a reduction was observed in total bilirubin (from 4.09 to 1.82 mg/dL; P <0.001), γ-glutamyl transpeptidase (P = 0.015), triglycerides (P = 0.03) and total cholesterol (P = 0.05). No significant changes in CD4 T cell count and no increases in viral load were observed 12 months after unboosting. Plasma drug monitoring after ritonavir removal revealed the presence of therapeutic atazanavir concentrations in all patients except one with poor therapy adherence. Conclusions: UGT1A1*28 is significantly related to hyperbilirubinaemia in HIV-1 patients receiving atazanavir. Genotyping before the initiation of antiretroviral therapy can reduce the emergence of severe hyperbilirubinaemia. Unboosted atazanavir-containing therapy is safe and efficacious in patients with an undetectable viral load with a UGT1A1*28 polymorphism, allowing the use of atazanavir in patients otherwise likely unable to receive it.

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