Abstract
Objectives The uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1)*28 allele in HIV-positive patients receiving atazanavir (ATV) might be associated with the risk of hyperbilirubinemia. Owing to mixed and inconclusive results, a meta-analysis was conducted to systematically summarize and clarify this association.Methods Based on a comprehensive search of PubMed, Embase and Web of Science databases, studies investigating the association between UGT1A1 alleles and hyperbilirubinemia was retrieved. We evaluated the strength of this relationship using odds ratios (ORs) with 95% confidence intervals (CIs). Sensitivity analysis was performed by removing each study one at a time and calculating the pooled ORs of the remaining studies to test the robustness of the meta-analysis results. The Q statistic and the I2 index statistic were used to assess heterogeneity. Publication bias was evaluated using Orwin’s fail-safe N test.Results A total of six individual studies were included in this meta-analysis. A significantly increased risk of hyperbilirubinemia was observed in HIV-positive patients receiving ATV with the UGT1A1*1/*28 or UGT1A1*28/*28 genotype, and the risk was higher with the UGT1A1*28/*28 genotype than with the UGT1A1*1/*28 genotype. (UGT1A1*28/*28 versus UGT1A1*1/*28: OR = 3.69, 95%CI = 1.82–7.49; UGT1A1*1/*28 versus UGT1A1*1/*1: OR = 3.50, 95%CI = 1.35–9.08; UGT1A1*28/*28 versus UGT1A1*1/*1: OR = 10.07, 95%CI = 4.39–23.10). All of the pooled ORs were not significantly affected by the remaining studies and different modeling methods, indicating robust results.Conclusions This meta-analysis suggests that the UGT1A1*28 allele represents a biomarker for an increased risk of hyperbilirubinemia in HIV-positive patients receiving ATV.
Highlights
Atazanavir (ATV) is currently one of the most widely used protease inhibitors in the treatment of HIV infection
If I2 > 50% or P
Hyperbilirubinemia severity was classified on the basis of the AIDS Clinical Trial Group guidelines [37] for total bilirubin levels as follows: grade 1, 23–32 μM (1.3–1.9 mg/dl); grade 2, 33–53 μM (1.9–3.1 mg/dl); grade 3, 54–105 μM (3.1–6.1 mg/dl); and grade 4, >105 μM (>6.1 mg/dl)
Summary
Atazanavir (ATV) is currently one of the most widely used protease inhibitors in the treatment of HIV infection. It displays several advantages over other protease inhibitors, such as a favorable lipid profile, once daily dosing, low capsule burden, and a relatively distinct resistance profile [1]. The most frequent adverse effect associated with ATV use is an elevation of bilirubin. ATV causes hyperbilirubinemia due to inhibition of the enzyme uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1), which is involved in the bilirubin conjugation [2]. The risk of hyperbilirubinemia is dependent on ATV plasma concentrations as well as genetic factors influencing UGT1A1 function [3,4]. An outstanding example is the glucuronidation and disposition to the side effects of the License 4.0 (CC BY)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
