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Association between the UGT1A1*28 allele and hyperbilirubinemia in HIV-positive patients receiving atazanavir: a meta-analysis.

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.

SUBMITTER: Du P

PROVIDER: S-EPMC6499501 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Association between the UGT1A1*28 allele and hyperbilirubinemia in HIV-positive patients receiving atazanavir: a meta-analysis.

Du Pengqiang P Wang Aifeng A Ma Yongcheng Y Li Xingang X

Bioscience reports 20190502 5

<b>Objectives</b> 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.<b>Methods</b> Based on a comprehensive search of PubMed, Embase and Web of Science databases, studies investigating the association between UGT1A1 alleles and hyperbilirubin ...[more]

PMID: 30962262

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Project description:ObjectivePatients with HIV infection have an increased risk of cardiovascular disease compared with uninfected individuals. Antiretroviral therapy with atazanavir (ATV) delays progression of atherosclerosis markers; whether this reduces cardiovascular disease event risk compared with other antiretroviral regimens is currently unknown.DesignPopulation-based, noninterventional, historical cohort study conducted from 1 July 2003 through 31 December 2015.SettingVeterans Health Administration hospitals and clinics throughout the United States.ParticipantsTreatment-naive patients with HIV infection (N = 9500).Antiretroviral exposuresInitiating antiretroviral regimens containing ATV, other protease inhibitors, nonnucleoside reverse transcriptase inhibitors (NNRTIs), or integrase strand transfer inhibitors (INSTIs).Main outcome/effect size measuresIncidence rates of myocardial infarction (MI), stroke, and all-cause mortality within each regimen. ATV versus other protease inhibitor, NNRTI, or INSTI covariate-adjusted hazard ratios by using Cox proportional hazards models and inverse probability of treatment weighting.ResultsIncidence rates for MI, stroke, and all-cause mortality with ATV-containing regimens (5.2, 10.4, and 16.0 per 1000 patient-years, respectively) were lower than with regimens containing other protease inhibitors (10.2, 21.9, and 23.3 per 1000 patient-years), NNRTIs (7.5, 15.9, and 17.5 per 1000 patient-years), or INSTIs (13.0, 33.1, and 21.5 per 1000 patient-years). After inverse probability of treatment weighting, adjusted hazard ratios (95% confidence intervals) for MI, stroke, and all-cause mortality with ATV-containing regimens versus all non-ATV-containing regimens were 0.59 (0.41-0.84), 0.64 (0.50-0.81), and 0.90 (0.73-1.11), respectively.ConclusionAmong treatment-naive HIV-infected patients in the Veterans Health Administration initiating ATV-containing regimens, risk of both MI and stroke were significantly lower than in those initiating regimens containing other protease inhibitors, NNRTIs, or INSTIs.

Dataset Information

Association between the UGT1A1*28 allele and hyperbilirubinemia in HIV-positive patients receiving atazanavir: a meta-analysis.

Publications

Association between the UGT1A1*28 allele and hyperbilirubinemia in HIV-positive patients receiving atazanavir: a meta-analysis.

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