Switching to unboosted atazanavir reduces bilirubin and triglycerides without compromising treatment efficacy in UGT1A1*28 polymorphism carriers.
OBJECTIVE
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.
Dipartimento Scienze Cliniche (DISC) L. Sacco Hospital-Infectious Diseases and Immunopathology Section,  Università di Milano, Milano,  Italy.
Laurenzia
L
Ferraris
Ottavia
O
Viganò
Anna
A
Peri
Maciej
M
Tarkowski
Greta
G
Milani
Stefano
S
Bonora
Fulvio
F
Adorni
Cristina
C
Gervasoni
Emilio
E
Clementi
Giovanni
G
Di Perri
Massimo
M
Galli
Agostino
A
Riva
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000069446:Atazanavir Sulfate; D001663:Bilirubin / Q000097:blood*; D005260:Female; D014453:Glucuronosyltransferase / Q000235:genetics*; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage* / Q000009:adverse effects*; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects*; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood*; D000099148:UGT1A1 Enzyme
D019380:Anti-HIV Agents; D000069446:Atazanavir Sulfate; D001663:Bilirubin; D014453:Glucuronosyltransferase; D009842:Oligopeptides; D011725:Pyridines; D014280:Triglycerides; D000099148:UGT1A1 Enzyme