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- Title
Switching to unboosted atazanavir reduces bilirubin and triglycerides without compromising treatment efficacy in UGT1A1*28 polymorphism carriers.
- Authors
Ferraris, Laurenzia; Viganò, Ottavia; Peri, Anna; Tarkowski, Maciej; Milani, Greta; Bonora, Stefano; Adorni, Fulvio; Gervasoni, Cristina; Clementi, Emilio; Di Perri, Giovanni; Galli, Massimo; Riva, Agostino
- 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.
- Subjects
ATAZANAVIR; BILIRUBIN; TRIGLYCERIDES; ANTIRETROVIRAL agents; PHARMACOGENOMICS; DRUG monitoring research
- Publication
Journal of Antimicrobial Chemotherapy (JAC), 2012, Vol 67, Issue 9, p2236
- ISSN
0305-7453
- Publication type
Article
- DOI
10.1093/jac/dks175