Clinical and genetic factors associated with increased risk of severe liver toxicity in a monocentric cohort of HIV positive patients receiving nevirapine-based antiretroviral therapy
Nevirapine has been used as antiretroviral agent since early '90. Although nevirapine is not currently recommended in initial anti-HIV regimens, its use remains consistent in a certain number of HIV-1-positive subjects. Thus, our aim was to determine clinical and genetic factors involved in the...
Saved in:
| Published in | BMC infectious diseases Vol. 18; no. 1; pp. 556 - 8 |
|---|---|
| Main Authors | , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
England
BioMed Central Ltd
12.11.2018
BioMed Central BMC |
| Subjects | |
| Online Access | Get full text |
Cover
Loading…
| Abstract | Nevirapine has been used as antiretroviral agent since early '90. Although nevirapine is not currently recommended in initial anti-HIV regimens, its use remains consistent in a certain number of HIV-1-positive subjects. Thus, our aim was to determine clinical and genetic factors involved in the development of severe nevirapine induced liver toxicity.
We retrospectively analyzed all HIV positive patients who were followed at the Infectious Diseases Unit, DIBIC Luigi Sacco, University of Milan from May 2011 to December 2015. All patients treated with nevirapine who underwent a genotyping for the functional variants mapping into ABCB1, CYP2B6, CYP3A4 and CYP3A5 genes were included in the analysis. Severe hepatotoxicity was defined as ACTG grade 3-4 AST/ALT increase during the first three months of nevirapine treatment. The causality assessment between NVP exposure and drug-induced liver injury was performed by using the updated Roussel Uclaf Causality Assessment Methods. Hardy Weinberg equilibrium was tested by χ
test. A multivariable logistic regression model was constructed using a backward elimination method.
Three hundred and sixty-two patients were included in the analysis, of which 8 (2.2%) experienced a severe liver toxicity. We observed no differences between patients with and without liver toxicity as regards gender, ethnicity, age and immune-virological status. A higher prevalence of HCV coinfection (75.0% vs 30.2%; p = .0013) and higher baseline AST (58 IU/L vs 26 IU/L; p = 0.041) and ALT (82 IU/L vs 27 IU/L; p = 0.047) median levels were observed in patients with liver toxicity vs those without toxicity. The genotypes CT/TT at ABCB1 rs1045642 single nucleotide polymorphism (SNP), showed a protective effect for liver toxicity when compared with genotype CC (OR = 0.18, 95%CI 0.04-0.76; p = 0.020) in univariate analysis. In the multivariate model, HCV coinfection was independently associated with higher risk of developing liver toxicity (aOR = 8.00, 95%CI 1.27-50.29; p = 0.027), whereas ABCB1 rs1045642 CT/TT genotypes (aOR = 0.10, 95%CI 0.02-0.47; p = 0.004) was associated with a lower risk.
According to our findings HCV coinfection and ABCB1 rs1045642 SNP represent independent determinants of severe liver toxicity related to nevirapine. This genetic evaluation could be included as toxicity assessment in HIV-1-positive subjects treated with nevirapine. |
|---|---|
| AbstractList | Nevirapine has been used as antiretroviral agent since early '90. Although nevirapine is not currently recommended in initial anti-HIV regimens, its use remains consistent in a certain number of HIV-1-positive subjects. Thus, our aim was to determine clinical and genetic factors involved in the development of severe nevirapine induced liver toxicity. We retrospectively analyzed all HIV positive patients who were followed at the Infectious Diseases Unit, DIBIC Luigi Sacco, University of Milan from May 2011 to December 2015. All patients treated with nevirapine who underwent a genotyping for the functional variants mapping into ABCB1, CYP2B6, CYP3A4 and CYP3A5 genes were included in the analysis. Severe hepatotoxicity was defined as ACTG grade 3-4 AST/ALT increase during the first three months of nevirapine treatment. The causality assessment between NVP exposure and drug-induced liver injury was performed by using the updated Roussel Uclaf Causality Assessment Methods. Hardy Weinberg equilibrium was tested by [chl].sup.2 test. A multivariable logistic regression model was constructed using a backward elimination method. Three hundred and sixty-two patients were included in the analysis, of which 8 (2.2%) experienced a severe liver toxicity. We observed no differences between patients with and without liver toxicity as regards gender, ethnicity, age and immune-virological status. A higher prevalence of HCV coinfection (75.0% vs 30.2%; p = .0013) and higher baseline AST (58 IU/L vs 26 IU/L; p = 0.041) and ALT (82 IU/L vs 27 IU/L; p = 0.047) median levels were observed in patients with liver toxicity vs those without toxicity. The genotypes CT/TT at ABCB1 rs1045642 single nucleotide polymorphism (SNP), showed a protective effect for liver toxicity when compared with genotype CC (OR = 0.18, 95%CI 0.04-0.76; p = 0.020) in univariate analysis. In the multivariate model, HCV coinfection was independently associated with higher risk of developing liver toxicity (aOR = 8.00, 95%CI 1.27-50.29; p = 0.027), whereas ABCB1 rs1045642 CT/TT genotypes (aOR = 0.10, 95%CI 0.02-0.47; p = 0.004) was associated with a lower risk. According to our findings HCV coinfection and ABCB1 rs1045642 SNP represent independent determinants of severe liver toxicity related to nevirapine. This genetic evaluation could be included as toxicity assessment in HIV-1-positive subjects treated with nevirapine. Nevirapine has been used as antiretroviral agent since early '90. Although nevirapine is not currently recommended in initial anti-HIV regimens, its use remains consistent in a certain number of HIV-1-positive subjects. Thus, our aim was to determine clinical and genetic factors involved in the development of severe nevirapine induced liver toxicity. We retrospectively analyzed all HIV positive patients who were followed at the Infectious Diseases Unit, DIBIC Luigi Sacco, University of Milan from May 2011 to December 2015. All patients treated with nevirapine who underwent a genotyping for the functional variants mapping into ABCB1, CYP2B6, CYP3A4 and CYP3A5 genes were included in the analysis. Severe hepatotoxicity was defined as ACTG grade 3-4 AST/ALT increase during the first three months of nevirapine treatment. The causality assessment between NVP exposure and drug-induced liver injury was performed by using the updated Roussel Uclaf Causality Assessment Methods. Hardy Weinberg equilibrium was tested by χ test. A multivariable logistic regression model was constructed using a backward elimination method. Three hundred and sixty-two patients were included in the analysis, of which 8 (2.2%) experienced a severe liver toxicity. We observed no differences between patients with and without liver toxicity as regards gender, ethnicity, age and immune-virological status. A higher prevalence of HCV coinfection (75.0% vs 30.2%; p = .0013) and higher baseline AST (58 IU/L vs 26 IU/L; p = 0.041) and ALT (82 IU/L vs 27 IU/L; p = 0.047) median levels were observed in patients with liver toxicity vs those without toxicity. The genotypes CT/TT at ABCB1 rs1045642 single nucleotide polymorphism (SNP), showed a protective effect for liver toxicity when compared with genotype CC (OR = 0.18, 95%CI 0.04-0.76; p = 0.020) in univariate analysis. In the multivariate model, HCV coinfection was independently associated with higher risk of developing liver toxicity (aOR = 8.00, 95%CI 1.27-50.29; p = 0.027), whereas ABCB1 rs1045642 CT/TT genotypes (aOR = 0.10, 95%CI 0.02-0.47; p = 0.004) was associated with a lower risk. According to our findings HCV coinfection and ABCB1 rs1045642 SNP represent independent determinants of severe liver toxicity related to nevirapine. This genetic evaluation could be included as toxicity assessment in HIV-1-positive subjects treated with nevirapine. Background Nevirapine has been used as antiretroviral agent since early '90. Although nevirapine is not currently recommended in initial anti-HIV regimens, its use remains consistent in a certain number of HIV-1-positive subjects. Thus, our aim was to determine clinical and genetic factors involved in the development of severe nevirapine induced liver toxicity. Methods We retrospectively analyzed all HIV positive patients who were followed at the Infectious Diseases Unit, DIBIC Luigi Sacco, University of Milan from May 2011 to December 2015. All patients treated with nevirapine who underwent a genotyping for the functional variants mapping into ABCB1, CYP2B6, CYP3A4 and CYP3A5 genes were included in the analysis. Severe hepatotoxicity was defined as ACTG grade 3-4 AST/ALT increase during the first three months of nevirapine treatment. The causality assessment between NVP exposure and drug-induced liver injury was performed by using the updated Roussel Uclaf Causality Assessment Methods. Hardy Weinberg equilibrium was tested by [chl].sup.2 test. A multivariable logistic regression model was constructed using a backward elimination method. Results Three hundred and sixty-two patients were included in the analysis, of which 8 (2.2%) experienced a severe liver toxicity. We observed no differences between patients with and without liver toxicity as regards gender, ethnicity, age and immune-virological status. A higher prevalence of HCV coinfection (75.0% vs 30.2%; p = .0013) and higher baseline AST (58 IU/L vs 26 IU/L; p = 0.041) and ALT (82 IU/L vs 27 IU/L; p = 0.047) median levels were observed in patients with liver toxicity vs those without toxicity. The genotypes CT/TT at ABCB1 rs1045642 single nucleotide polymorphism (SNP), showed a protective effect for liver toxicity when compared with genotype CC (OR = 0.18, 95%CI 0.04-0.76; p = 0.020) in univariate analysis. In the multivariate model, HCV coinfection was independently associated with higher risk of developing liver toxicity (aOR = 8.00, 95%CI 1.27-50.29; p = 0.027), whereas ABCB1 rs1045642 CT/TT genotypes (aOR = 0.10, 95%CI 0.02-0.47; p = 0.004) was associated with a lower risk. Conclusions According to our findings HCV coinfection and ABCB1 rs1045642 SNP represent independent determinants of severe liver toxicity related to nevirapine. This genetic evaluation could be included as toxicity assessment in HIV-1-positive subjects treated with nevirapine. Keywords: Nevirapine, Pharmacogenetic, Hepatotoxicity, ABCB1 Background Nevirapine has been used as antiretroviral agent since early ‘90. Although nevirapine is not currently recommended in initial anti-HIV regimens, its use remains consistent in a certain number of HIV-1-positive subjects. Thus, our aim was to determine clinical and genetic factors involved in the development of severe nevirapine induced liver toxicity. Methods We retrospectively analyzed all HIV positive patients who were followed at the Infectious Diseases Unit, DIBIC Luigi Sacco, University of Milan from May 2011 to December 2015. All patients treated with nevirapine who underwent a genotyping for the functional variants mapping into ABCB1, CYP2B6, CYP3A4 and CYP3A5 genes were included in the analysis. Severe hepatotoxicity was defined as ACTG grade 3–4 AST/ALT increase during the first three months of nevirapine treatment. The causality assessment between NVP exposure and drug-induced liver injury was performed by using the updated Roussel Uclaf Causality Assessment Methods. Hardy Weinberg equilibrium was tested by χ2 test. A multivariable logistic regression model was constructed using a backward elimination method. Results Three hundred and sixty-two patients were included in the analysis, of which 8 (2.2%) experienced a severe liver toxicity. We observed no differences between patients with and without liver toxicity as regards gender, ethnicity, age and immune-virological status. A higher prevalence of HCV coinfection (75.0% vs 30.2%; p = .0013) and higher baseline AST (58 IU/L vs 26 IU/L; p = 0.041) and ALT (82 IU/L vs 27 IU/L; p = 0.047) median levels were observed in patients with liver toxicity vs those without toxicity. The genotypes CT/TT at ABCB1 rs1045642 single nucleotide polymorphism (SNP), showed a protective effect for liver toxicity when compared with genotype CC (OR = 0.18, 95%CI 0.04–0.76; p = 0.020) in univariate analysis. In the multivariate model, HCV coinfection was independently associated with higher risk of developing liver toxicity (aOR = 8.00, 95%CI 1.27–50.29; p = 0.027), whereas ABCB1 rs1045642 CT/TT genotypes (aOR = 0.10, 95%CI 0.02–0.47; p = 0.004) was associated with a lower risk. Conclusions According to our findings HCV coinfection and ABCB1 rs1045642 SNP represent independent determinants of severe liver toxicity related to nevirapine. This genetic evaluation could be included as toxicity assessment in HIV-1-positive subjects treated with nevirapine. Abstract Background Nevirapine has been used as antiretroviral agent since early ‘90. Although nevirapine is not currently recommended in initial anti-HIV regimens, its use remains consistent in a certain number of HIV-1-positive subjects. Thus, our aim was to determine clinical and genetic factors involved in the development of severe nevirapine induced liver toxicity. Methods We retrospectively analyzed all HIV positive patients who were followed at the Infectious Diseases Unit, DIBIC Luigi Sacco, University of Milan from May 2011 to December 2015. All patients treated with nevirapine who underwent a genotyping for the functional variants mapping into ABCB1, CYP2B6, CYP3A4 and CYP3A5 genes were included in the analysis. Severe hepatotoxicity was defined as ACTG grade 3–4 AST/ALT increase during the first three months of nevirapine treatment. The causality assessment between NVP exposure and drug-induced liver injury was performed by using the updated Roussel Uclaf Causality Assessment Methods. Hardy Weinberg equilibrium was tested by χ2 test. A multivariable logistic regression model was constructed using a backward elimination method. Results Three hundred and sixty-two patients were included in the analysis, of which 8 (2.2%) experienced a severe liver toxicity. We observed no differences between patients with and without liver toxicity as regards gender, ethnicity, age and immune-virological status. A higher prevalence of HCV coinfection (75.0% vs 30.2%; p = .0013) and higher baseline AST (58 IU/L vs 26 IU/L; p = 0.041) and ALT (82 IU/L vs 27 IU/L; p = 0.047) median levels were observed in patients with liver toxicity vs those without toxicity. The genotypes CT/TT at ABCB1 rs1045642 single nucleotide polymorphism (SNP), showed a protective effect for liver toxicity when compared with genotype CC (OR = 0.18, 95%CI 0.04–0.76; p = 0.020) in univariate analysis. In the multivariate model, HCV coinfection was independently associated with higher risk of developing liver toxicity (aOR = 8.00, 95%CI 1.27–50.29; p = 0.027), whereas ABCB1 rs1045642 CT/TT genotypes (aOR = 0.10, 95%CI 0.02–0.47; p = 0.004) was associated with a lower risk. Conclusions According to our findings HCV coinfection and ABCB1 rs1045642 SNP represent independent determinants of severe liver toxicity related to nevirapine. This genetic evaluation could be included as toxicity assessment in HIV-1-positive subjects treated with nevirapine. Nevirapine has been used as antiretroviral agent since early '90. Although nevirapine is not currently recommended in initial anti-HIV regimens, its use remains consistent in a certain number of HIV-1-positive subjects. Thus, our aim was to determine clinical and genetic factors involved in the development of severe nevirapine induced liver toxicity.BACKGROUNDNevirapine has been used as antiretroviral agent since early '90. Although nevirapine is not currently recommended in initial anti-HIV regimens, its use remains consistent in a certain number of HIV-1-positive subjects. Thus, our aim was to determine clinical and genetic factors involved in the development of severe nevirapine induced liver toxicity.We retrospectively analyzed all HIV positive patients who were followed at the Infectious Diseases Unit, DIBIC Luigi Sacco, University of Milan from May 2011 to December 2015. All patients treated with nevirapine who underwent a genotyping for the functional variants mapping into ABCB1, CYP2B6, CYP3A4 and CYP3A5 genes were included in the analysis. Severe hepatotoxicity was defined as ACTG grade 3-4 AST/ALT increase during the first three months of nevirapine treatment. The causality assessment between NVP exposure and drug-induced liver injury was performed by using the updated Roussel Uclaf Causality Assessment Methods. Hardy Weinberg equilibrium was tested by χ2 test. A multivariable logistic regression model was constructed using a backward elimination method.METHODSWe retrospectively analyzed all HIV positive patients who were followed at the Infectious Diseases Unit, DIBIC Luigi Sacco, University of Milan from May 2011 to December 2015. All patients treated with nevirapine who underwent a genotyping for the functional variants mapping into ABCB1, CYP2B6, CYP3A4 and CYP3A5 genes were included in the analysis. Severe hepatotoxicity was defined as ACTG grade 3-4 AST/ALT increase during the first three months of nevirapine treatment. The causality assessment between NVP exposure and drug-induced liver injury was performed by using the updated Roussel Uclaf Causality Assessment Methods. Hardy Weinberg equilibrium was tested by χ2 test. A multivariable logistic regression model was constructed using a backward elimination method.Three hundred and sixty-two patients were included in the analysis, of which 8 (2.2%) experienced a severe liver toxicity. We observed no differences between patients with and without liver toxicity as regards gender, ethnicity, age and immune-virological status. A higher prevalence of HCV coinfection (75.0% vs 30.2%; p = .0013) and higher baseline AST (58 IU/L vs 26 IU/L; p = 0.041) and ALT (82 IU/L vs 27 IU/L; p = 0.047) median levels were observed in patients with liver toxicity vs those without toxicity. The genotypes CT/TT at ABCB1 rs1045642 single nucleotide polymorphism (SNP), showed a protective effect for liver toxicity when compared with genotype CC (OR = 0.18, 95%CI 0.04-0.76; p = 0.020) in univariate analysis. In the multivariate model, HCV coinfection was independently associated with higher risk of developing liver toxicity (aOR = 8.00, 95%CI 1.27-50.29; p = 0.027), whereas ABCB1 rs1045642 CT/TT genotypes (aOR = 0.10, 95%CI 0.02-0.47; p = 0.004) was associated with a lower risk.RESULTSThree hundred and sixty-two patients were included in the analysis, of which 8 (2.2%) experienced a severe liver toxicity. We observed no differences between patients with and without liver toxicity as regards gender, ethnicity, age and immune-virological status. A higher prevalence of HCV coinfection (75.0% vs 30.2%; p = .0013) and higher baseline AST (58 IU/L vs 26 IU/L; p = 0.041) and ALT (82 IU/L vs 27 IU/L; p = 0.047) median levels were observed in patients with liver toxicity vs those without toxicity. The genotypes CT/TT at ABCB1 rs1045642 single nucleotide polymorphism (SNP), showed a protective effect for liver toxicity when compared with genotype CC (OR = 0.18, 95%CI 0.04-0.76; p = 0.020) in univariate analysis. In the multivariate model, HCV coinfection was independently associated with higher risk of developing liver toxicity (aOR = 8.00, 95%CI 1.27-50.29; p = 0.027), whereas ABCB1 rs1045642 CT/TT genotypes (aOR = 0.10, 95%CI 0.02-0.47; p = 0.004) was associated with a lower risk.According to our findings HCV coinfection and ABCB1 rs1045642 SNP represent independent determinants of severe liver toxicity related to nevirapine. This genetic evaluation could be included as toxicity assessment in HIV-1-positive subjects treated with nevirapine.CONCLUSIONSAccording to our findings HCV coinfection and ABCB1 rs1045642 SNP represent independent determinants of severe liver toxicity related to nevirapine. This genetic evaluation could be included as toxicity assessment in HIV-1-positive subjects treated with nevirapine. |
| ArticleNumber | 556 |
| Audience | Academic |
| Author | Rusconi, Stefano Oreni, Maria Letizia Cheli, Stefania Lupo, Angelica Giacomelli, Andrea Renisi, Giulia Ridolfo, Anna Lisa Clementi, Emilio Riva, Agostino Falvella, Felicia Stefania Cattaneo, Dario Di Cristo, Valentina Galli, Massimo |
| Author_xml | – sequence: 1 givenname: Andrea orcidid: 0000-0003-3685-4289 surname: Giacomelli fullname: Giacomelli, Andrea – sequence: 2 givenname: Agostino surname: Riva fullname: Riva, Agostino – sequence: 3 givenname: Felicia Stefania surname: Falvella fullname: Falvella, Felicia Stefania – sequence: 4 givenname: Maria Letizia surname: Oreni fullname: Oreni, Maria Letizia – sequence: 5 givenname: Dario surname: Cattaneo fullname: Cattaneo, Dario – sequence: 6 givenname: Stefania surname: Cheli fullname: Cheli, Stefania – sequence: 7 givenname: Giulia surname: Renisi fullname: Renisi, Giulia – sequence: 8 givenname: Valentina surname: Di Cristo fullname: Di Cristo, Valentina – sequence: 9 givenname: Angelica surname: Lupo fullname: Lupo, Angelica – sequence: 10 givenname: Emilio surname: Clementi fullname: Clementi, Emilio – sequence: 11 givenname: Stefano surname: Rusconi fullname: Rusconi, Stefano – sequence: 12 givenname: Massimo surname: Galli fullname: Galli, Massimo – sequence: 13 givenname: Anna Lisa surname: Ridolfo fullname: Ridolfo, Anna Lisa |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/30419834$$D View this record in MEDLINE/PubMed |
| BookMark | eNqNk89u1DAQxiNURNuFB-CCLHEph5Q4TuLkglRVQFeqVIk_vVpeZ7w7JWsvtndpn4zXY9JtoVuBRKLIzvg3n-XPM4fZnvMOsuwlL445b5u3kZet7PKCt7momjKvn2QHvJI8L4Wo9h7M97PDGK-Kgsu27J5l-6KoeNeK6iD7eTqgQ6MHpl3P5uAgoWFWm-RDZDpGb1An6NkPTAuGzgTQkX4Dxm_MWxZhAwHYgDSw5K_RYLohjmm29M4bcCmQoPELH9KYcDa9ZCsfMVEGW-mEREQWwABu0M2Zgw0GvUIH-ex2J-0SBkjBj_GBpQXQ8s3z7KnVQ4QXd-Mk-_rh_ZfTs_z84uP09OQ8N03Zplx0fd9VFRcgZj1UJUgBXSWkEbaowIpamrZpO2P5rDRtV5M9dWfbopOltaY3YpJNt7q911dqFXCpw43yGtVtwIe50oEsG0A1rZZ1weu67PpK9xWpzeiTtp8VYnwm2but1mo9W0J_640edkR3Vxwu1NxvVEN3WNMhJtnRnUDw39cQk1piNDAM2oFfR1VyUcpS0i0T-voReuXXwZFVI1Vz0UlR_6Hmmg6Aznra14yi6qRuWiqsRkqijv9C0dvDEg2VpEWK7yS82UkgJsF1mut1jGr6-dP_sxeXu-yrhwb-du6-nAmQW8AEH2MAq6gcqcb86CcOihdqbBy1bRxFsmpsHDU6wR9l3ov_O-cXSBobgA |
| CitedBy_id | crossref_primary_10_3389_fphar_2019_00730 crossref_primary_10_3390_ijms241310855 crossref_primary_10_3390_jcm11226620 crossref_primary_10_3389_fmed_2022_817370 crossref_primary_10_1186_s12879_025_10538_w crossref_primary_10_1093_toxsci_kfae054 crossref_primary_10_3390_cells10071687 crossref_primary_10_3390_medicines11040009 crossref_primary_10_1016_j_bcp_2022_115224 crossref_primary_10_1021_acs_molpharmaceut_9b00871 crossref_primary_10_1002_jbt_70174 crossref_primary_10_1007_s40278_019_58408_1 crossref_primary_10_3390_livers3030030 crossref_primary_10_1038_s41598_024_79965_0 |
| Cites_doi | 10.1111/j.1468-1293.2012.00995.x 10.1086/428093 10.1097/00126334-200402010-00003 10.1086/507097 10.1093/jac/dkp044 10.1111/j.1468-1293.2008.00689.x 10.3390/ijms17010014 10.1086/381450 10.1097/FPC.0b013e32835a5af2 10.1111/j.1742-7843.2011.00780.x 10.5402/2012/932542 10.1310/hct1102-110 10.1097/QAD.0b013e32834779df 10.1016/j.jhep.2005.11.027 10.1177/2050312118780861 10.1097/QAD.0b013e32832d3b54 10.1124/dmd.108.024851 10.1111/j.1468-1293.2007.00432.x 10.1016/j.pharmthera.2012.12.007 10.1093/jac/dkr087 10.1001/jama.283.1.74 10.2217/pgs.09.142 10.1093/jac/dkn029 10.1371/journal.pone.0128131 10.1097/01.fpc.0000236338.41799.57 10.1097/01213011-200501000-00001 10.1177/135965350701200305 10.1371/journal.pone.0171596 10.1097/00126334-200309011-00005 10.1586/14787210.2.3.367 10.1097/MD.0000000000004890 10.1515/dmdi-2012-0031 |
| ContentType | Journal Article |
| Copyright | COPYRIGHT 2018 BioMed Central Ltd. Copyright © 2018. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. The Author(s). 2018 |
| Copyright_xml | – notice: COPYRIGHT 2018 BioMed Central Ltd. – notice: Copyright © 2018. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. – notice: The Author(s). 2018 |
| DBID | AAYXX CITATION CGR CUY CVF ECM EIF NPM IOV ISR 3V. 7QL 7T2 7U9 7X7 7XB 88E 8C1 8FI 8FJ 8FK ABUWG AEUYN AFKRA AZQEC BENPR C1K CCPQU DWQXO FYUFA GHDGH H94 K9. M0S M1P M7N PHGZM PHGZT PIMPY PJZUB PKEHL PPXIY PQEST PQQKQ PQUKI 7X8 5PM DOA |
| DOI | 10.1186/s12879-018-3462-5 |
| DatabaseTitle | CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) Publicly Available Content Database ProQuest One Academic Middle East (New) ProQuest Central Essentials ProQuest Health & Medical Complete (Alumni) ProQuest Central (Alumni Edition) ProQuest One Community College ProQuest One Health & Nursing Environmental Sciences and Pollution Management ProQuest Central ProQuest One Sustainability Health Research Premium Collection Health and Medicine Complete (Alumni Edition) ProQuest Central Korea Bacteriology Abstracts (Microbiology B) Algology Mycology and Protozoology Abstracts (Microbiology C) Health & Medical Research Collection AIDS and Cancer Research Abstracts Health & Safety Science Abstracts ProQuest Central (New) ProQuest Medical Library (Alumni) ProQuest Public Health Virology and AIDS Abstracts ProQuest One Academic Eastern Edition ProQuest Hospital Collection Health Research Premium Collection (Alumni) ProQuest Hospital Collection (Alumni) ProQuest Health & Medical Complete ProQuest Medical Library ProQuest One Academic UKI Edition ProQuest One Academic ProQuest One Academic (New) ProQuest Central (Alumni) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE Publicly Available Content Database MEDLINE - Academic |
| Database_xml | – sequence: 1 dbid: DOA name: DOAJ Directory of Open Access Journals url: https://www.doaj.org/ sourceTypes: Open Website – sequence: 2 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 3 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database – sequence: 4 dbid: BENPR name: ProQuest Central url: https://www.proquest.com/central sourceTypes: Aggregation Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Medicine |
| EISSN | 1471-2334 |
| EndPage | 8 |
| ExternalDocumentID | oai_doaj_org_article_68a75015529d4ad4958b9587fdb03333 PMC6233541 A568018677 30419834 10_1186_s12879_018_3462_5 |
| Genre | Journal Article |
| GroupedDBID | --- 0R~ 23N 2WC 53G 5VS 6J9 6PF 7X7 88E 8C1 8FI 8FJ AAFWJ AAJSJ AASML AAWTL AAYXX ABDBF ABUWG ACGFO ACGFS ACIHN ACPRK ACUHS ADBBV ADRAZ ADUKV AEAQA AENEX AEUYN AFKRA AFPKN AFRAH AHBYD AHMBA AHYZX ALIPV ALMA_UNASSIGNED_HOLDINGS AMKLP AMTXH AOIJS BAPOH BAWUL BCNDV BENPR BFQNJ BMC BPHCQ BVXVI C6C CCPQU CITATION CS3 DIK DU5 E3Z EAD EAP EAS EBD EBLON EBS EJD EMB EMK EMOBN ESX F5P FYUFA GROUPED_DOAJ GX1 H13 HMCUK HYE IAO IHR INH INR IOV ISR ITC KQ8 M1P M48 M~E O5R O5S OK1 OVT P2P PGMZT PHGZM PHGZT PIMPY PQQKQ PROAC PSQYO RBZ RNS ROL RPM RSV SMD SOJ SV3 TR2 TUS UKHRP W2D WOQ WOW XSB -A0 3V. ACRMQ ADINQ C24 CGR CUY CVF ECM EIF NPM PMFND 7QL 7T2 7U9 7XB 8FK AZQEC C1K DWQXO H94 K9. M7N PJZUB PKEHL PPXIY PQEST PQUKI 7X8 5PM PUEGO |
| ID | FETCH-LOGICAL-c628t-39dd94413e3bde42e73e9437c3f04ef357c8689cf1b2c89582959f80972ffcdc3 |
| IEDL.DBID | 7X7 |
| ISSN | 1471-2334 |
| IngestDate | Wed Aug 27 01:29:22 EDT 2025 Thu Aug 21 14:13:37 EDT 2025 Fri Jul 11 04:42:57 EDT 2025 Fri Jul 25 04:13:02 EDT 2025 Tue Jun 17 21:06:16 EDT 2025 Tue Jun 10 20:32:11 EDT 2025 Fri Jun 27 04:16:26 EDT 2025 Fri Jun 27 04:11:09 EDT 2025 Thu Jan 02 23:04:09 EST 2025 Thu Apr 24 23:01:45 EDT 2025 Tue Jul 01 01:57:32 EDT 2025 |
| IsDoiOpenAccess | true |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 1 |
| Keywords | Pharmacogenetic ABCB1 Nevirapine Hepatotoxicity |
| Language | English |
| License | Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c628t-39dd94413e3bde42e73e9437c3f04ef357c8689cf1b2c89582959f80972ffcdc3 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 |
| ORCID | 0000-0003-3685-4289 |
| OpenAccessLink | https://www.proquest.com/docview/2135139735?pq-origsite=%requestingapplication% |
| PMID | 30419834 |
| PQID | 2135139735 |
| PQPubID | 42582 |
| PageCount | 8 |
| ParticipantIDs | doaj_primary_oai_doaj_org_article_68a75015529d4ad4958b9587fdb03333 pubmedcentral_primary_oai_pubmedcentral_nih_gov_6233541 proquest_miscellaneous_2132727178 proquest_journals_2135139735 gale_infotracmisc_A568018677 gale_infotracacademiconefile_A568018677 gale_incontextgauss_ISR_A568018677 gale_incontextgauss_IOV_A568018677 pubmed_primary_30419834 crossref_citationtrail_10_1186_s12879_018_3462_5 crossref_primary_10_1186_s12879_018_3462_5 |
| ProviderPackageCode | CITATION AAYXX |
| PublicationCentury | 2000 |
| PublicationDate | 2018-11-12 |
| PublicationDateYYYYMMDD | 2018-11-12 |
| PublicationDate_xml | – month: 11 year: 2018 text: 2018-11-12 day: 12 |
| PublicationDecade | 2010 |
| PublicationPlace | England |
| PublicationPlace_xml | – name: England – name: London |
| PublicationTitle | BMC infectious diseases |
| PublicationTitleAlternate | BMC Infect Dis |
| PublicationYear | 2018 |
| Publisher | BioMed Central Ltd BioMed Central BMC |
| Publisher_xml | – name: BioMed Central Ltd – name: BioMed Central – name: BMC |
| References | M Rotger (3462_CR17) 2005; 15 P De Boissieu (3462_CR2) 2016; 95 DT Dieterich (3462_CR7) 2004; 38 J Bertrand (3462_CR14) 2012; 22 SR Penzak (3462_CR15) 2007; 8 JM Llibre (3462_CR4) 2015; 10 SM Patel (3462_CR5) 2004; 35 JO Stern (3462_CR6) 2003; 34 T Mahungu (3462_CR29) 2009; 10 C Gozalo (3462_CR18) 2011; 109 A Owen (3462_CR32) 2006; 16 AM Kesselring (3462_CR9) 2009; 23 MS Sulkowski (3462_CR25) 2000; 283 V Reliquet (3462_CR3) 2010; 11 A Schipani (3462_CR28) 2011; 66 PY Wu (3462_CR8) 2017; 12 Z Bekker (3462_CR23) 2012; 2012 J Yuan (3462_CR31) 2011; 25 I Sanne (3462_CR12) 2005; 191 B Wen (3462_CR27) 2009; 37 M Núñez (3462_CR24) 2006; 44 G Danan (3462_CR21) 2016; 17 B Van Welzen (3462_CR11) 2012; 13 A Giacomelli (3462_CR30) 2018; 6 P Riska (3462_CR13) 1999; 27 A Mocroft (3462_CR10) 2007; 12 A Milinkovic (3462_CR1) 2004; 2 C Ciccacci (3462_CR20) 2010; 11 M Vogel (3462_CR26) 2009; 63 UM Zanger (3462_CR33) 2013; 138 DW Haas (3462_CR19) 2006; 43 S Brück (3462_CR22) 2008; 13 C Wyen (3462_CR16) 2008; 61 JP Kitzmiller (3462_CR34) 2013; 28 |
| References_xml | – volume: 13 start-page: 448 issue: 7 year: 2012 ident: 3462_CR11 publication-title: HIV Med. doi: 10.1111/j.1468-1293.2012.00995.x – volume: 191 start-page: 825 issue: 6 year: 2005 ident: 3462_CR12 publication-title: J Infect Dis doi: 10.1086/428093 – volume: 35 start-page: 120 issue: 2 year: 2004 ident: 3462_CR5 publication-title: J Acquir Immune Defic Syndr doi: 10.1097/00126334-200402010-00003 – volume: 43 start-page: 783 year: 2006 ident: 3462_CR19 publication-title: Clin Infect Dis doi: 10.1086/507097 – volume: 63 start-page: 988 issue: 5 year: 2009 ident: 3462_CR26 publication-title: J Antimicrob Chemother doi: 10.1093/jac/dkp044 – volume: 10 start-page: 310 issue: 5 year: 2009 ident: 3462_CR29 publication-title: HIV Med. doi: 10.1111/j.1468-1293.2008.00689.x – volume: 17 start-page: 14 issue: 1 year: 2016 ident: 3462_CR21 publication-title: Int J Mol Sci doi: 10.3390/ijms17010014 – volume: 38 start-page: S80 issue: Suppl. 2 year: 2004 ident: 3462_CR7 publication-title: Clin Infect Dis doi: 10.1086/381450 – volume: 22 start-page: 868 issue: 12 year: 2012 ident: 3462_CR14 publication-title: Pharmacogenet Genomics doi: 10.1097/FPC.0b013e32835a5af2 – volume: 109 start-page: 513 year: 2011 ident: 3462_CR18 publication-title: Basic & Clinical Pharmacology & Toxicology doi: 10.1111/j.1742-7843.2011.00780.x – volume: 2012 year: 2012 ident: 3462_CR23 publication-title: ISRN Pharmaceutics doi: 10.5402/2012/932542 – volume: 27 start-page: 895 year: 1999 ident: 3462_CR13 publication-title: Drug Metab Dispos – volume: 11 start-page: 110 issue: 2 year: 2010 ident: 3462_CR3 publication-title: HIV Clin Trials doi: 10.1310/hct1102-110 – volume: 25 start-page: 1271 issue: 10 year: 2011 ident: 3462_CR31 publication-title: AIDS doi: 10.1097/QAD.0b013e32834779df – volume: 44 start-page: S132 issue: 1 Suppl year: 2006 ident: 3462_CR24 publication-title: J Hepatol doi: 10.1016/j.jhep.2005.11.027 – volume: 6 start-page: 205031211878086 year: 2018 ident: 3462_CR30 publication-title: SAGE Open Med doi: 10.1177/2050312118780861 – volume: 23 start-page: 1689 year: 2009 ident: 3462_CR9 publication-title: AIDS doi: 10.1097/QAD.0b013e32832d3b54 – volume: 37 start-page: 1557 issue: 7 year: 2009 ident: 3462_CR27 publication-title: Drug Metab Dispos doi: 10.1124/dmd.108.024851 – volume: 8 start-page: 86 issue: 2 year: 2007 ident: 3462_CR15 publication-title: HIV Med doi: 10.1111/j.1468-1293.2007.00432.x – volume: 138 start-page: 103 issue: 1 year: 2013 ident: 3462_CR33 publication-title: Pharmacol Ther doi: 10.1016/j.pharmthera.2012.12.007 – volume: 66 start-page: 1332 issue: 6 year: 2011 ident: 3462_CR28 publication-title: J Antimicrob Chemother doi: 10.1093/jac/dkr087 – volume: 283 start-page: 74 year: 2000 ident: 3462_CR25 publication-title: JAMA doi: 10.1001/jama.283.1.74 – volume: 11 start-page: 23 year: 2010 ident: 3462_CR20 publication-title: Pharmacogenomics doi: 10.2217/pgs.09.142 – volume: 61 start-page: 914 year: 2008 ident: 3462_CR16 publication-title: J Antimicrob Chemother doi: 10.1093/jac/dkn029 – volume: 10 issue: 6 year: 2015 ident: 3462_CR4 publication-title: PLoS One doi: 10.1371/journal.pone.0128131 – volume: 16 start-page: 693 year: 2006 ident: 3462_CR32 publication-title: Pharmacogenet Genomics doi: 10.1097/01.fpc.0000236338.41799.57 – volume: 15 start-page: 1 year: 2005 ident: 3462_CR17 publication-title: Pharmacogenet Genomics doi: 10.1097/01213011-200501000-00001 – volume: 12 start-page: 325 issue: 3 year: 2007 ident: 3462_CR10 publication-title: Antivir Ther doi: 10.1177/135965350701200305 – volume: 12 issue: 2 year: 2017 ident: 3462_CR8 publication-title: PLoS One doi: 10.1371/journal.pone.0171596 – volume: 34 start-page: S21 issue: Suppl. 1 year: 2003 ident: 3462_CR6 publication-title: J Acquir Immune Defic Syndr doi: 10.1097/00126334-200309011-00005 – volume: 2 start-page: 367 year: 2004 ident: 3462_CR1 publication-title: Expert Rev Anti-Infect Ther doi: 10.1586/14787210.2.3.367 – volume: 95 issue: 37 year: 2016 ident: 3462_CR2 publication-title: Medicine (Baltimore) doi: 10.1097/MD.0000000000004890 – volume: 13 start-page: 343 year: 2008 ident: 3462_CR22 publication-title: Eur J Med Res – volume: 28 start-page: 59 issue: 1 year: 2013 ident: 3462_CR34 publication-title: Drug Metabol Drug Interact doi: 10.1515/dmdi-2012-0031 |
| SSID | ssj0017829 |
| Score | 2.2859073 |
| Snippet | Nevirapine has been used as antiretroviral agent since early '90. Although nevirapine is not currently recommended in initial anti-HIV regimens, its use... Background Nevirapine has been used as antiretroviral agent since early '90. Although nevirapine is not currently recommended in initial anti-HIV regimens, its... Background Nevirapine has been used as antiretroviral agent since early ‘90. Although nevirapine is not currently recommended in initial anti-HIV regimens, its... Abstract Background Nevirapine has been used as antiretroviral agent since early ‘90. Although nevirapine is not currently recommended in initial anti-HIV... |
| SourceID | doaj pubmedcentral proquest gale pubmed crossref |
| SourceType | Open Website Open Access Repository Aggregation Database Index Database Enrichment Source |
| StartPage | 556 |
| SubjectTerms | ABCB1 Acquired immune deficiency syndrome Adult AIDS Anti-HIV Agents - administration & dosage Anti-HIV Agents - adverse effects Anti-Retroviral Agents - administration & dosage Anti-Retroviral Agents - adverse effects Antiretroviral agents Antiretroviral drugs Antiretroviral therapy Chemical and Drug Induced Liver Injury - epidemiology Chemical and Drug Induced Liver Injury - genetics Cytochrome Diagnosis Drug dosages Drug therapy Drug Therapy, Combination - adverse effects Enzymes Equilibrium methods Female Gene expression Gene mapping Gene polymorphism Genetic factors Genetic Predisposition to Disease Genomics Genotype & phenotype Genotypes Genotyping Hepatitis Hepatitis C virus Hepatotoxicity HIV HIV Infections - complications HIV Infections - drug therapy HIV Infections - epidemiology HIV Infections - genetics Human immunodeficiency virus Humans Immune system Infectious diseases Liver Male Metabolism Middle Aged Minority & ethnic groups Nevirapine Nevirapine - administration & dosage Nevirapine - adverse effects Patients Pharmacogenetic Polymorphism Population Regression analysis Regression models Retrospective Studies Risk assessment Risk Factors Severity of Illness Index Single-nucleotide polymorphism Studies Toxicity |
| Title | Clinical and genetic factors associated with increased risk of severe liver toxicity in a monocentric cohort of HIV positive patients receiving nevirapine-based antiretroviral therapy |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/30419834 https://www.proquest.com/docview/2135139735 https://www.proquest.com/docview/2132727178 https://pubmed.ncbi.nlm.nih.gov/PMC6233541 https://doaj.org/article/68a75015529d4ad4958b9587fdb03333 |
| Volume | 18 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwfV1fa9swEBdbC2MvY__rrQvaGAwGprEl29LTaEpLOmg3srWEvQhbkrtAsLPYGesn29fbnax4NWMNRODopMg63ekknX5HyFtRyoInuQxZImzIY25DmUgexlnKrc4SmxbOQfY8nV7wj_Nk7jfcGu9WudWJTlGbWuMe-UGMoeRg8mTJh9WPEKNG4emqD6Fxl-widBm6dGXzfsEVwewn_UlmJNKDBnRxht5BImQ8hTXYYC5ykP3_KuYbM9PQa_LGNHTykDzw9iM97Bj-iNyx1WNy78yfkD8hvz3Q55LmlaEwOvCSIvVRdWjumWENxQ1YuqjQaGzgEV3MaV1SmCjt2tIlumvQtv4F1bbXQEdzCj1Qu1ZBhRhXd91igenpJe08v35a6lFaGwp61C5wr4JWzo14BY0LC_dPwEpQsy1uZcD70e4C2PVTcnFy_PVoGvrgDKFOY9GGTBojwZZilhXG8thmzErOMs3KMbclSzItUiF1GRWxFsCbGMZAKRAtqCy10ewZ2anqyu4RKiOuU2MjqMRyLUyBGIcFz_JMG5PnNiDjLZuU9sjlGEBjqdwKRqSq46wCzirkrEoC8r4vsupgO24jniDve0JE3HY_1Osr5QVYpSIH4woB66ThuYF1pSjgm5WmGDP4BOQNjhyFmBoVOu1c5ZumUaefLtVhkoIdgMCB_yP6MhsQvfNEZQ2vqXN_UQI6C7G6BpT7A0rQDHqYvR3FymumRv2Vo4C87rOxJHrbVbbeOJoY7FqQn4A87wZ93zlszCMpGA9INhCHQe8Nc6rFd4dbDpY2S3j04vZmvST3YxRRdLWM98lOu97YV2D4tcXISTek4igakd3J8fnn2chtokB6xgWks8m3P0JPX4g |
| linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV3db9MwELfGkIAXxDeBAQaBkJCiNbaT2A8IjY-pZR9IsE198xLbGZWqZDQp0H-KV_497hK3LELsbZX60PrsOL7z3dk-_46Q57JQuYgzFfJYulAw4UIVKxGyNBHOpLFL8jZAdj8ZHoqP43i8Rn4t78JgWOVSJ7aK2lYG98g3GaaSA-PJ4zen30LMGoWnq8sUGp1Y7LjFD1iy1a9H74G_Lxjb_nDwbhj6rAKhSZhsQq6sVeAEcMdz6wRzKXdK8NTwYiBcwePUyEQqU0Q5M1LFkkHnC4kwN0VhrOHQ7iVyGQzvAGdUOl4t8CKwtsqfnEYy2axB96cYjSRDLhJY8_VsX5si4F9DcMYS9qM0z5i97RvkuvdX6VYnYDfJmitvkSt7_kT-NvntgUWnNCstBWnES5HUZ_GhmWe-sxQ3fOmkRCe1hp8Y0k6rgoJhdjNHpxgeQpvqJzTbLICOZhRGvGp7BQ1iHt9ZgxWGoyPaRZp9d9SjwtYU9Lab4N4ILduw5VPoXJi3TwLRAbXe4NYJvB_tLpwt7pDDC2HbXbJeVqW7T6iKhEmsi6ARJ4y0OWIq5iLNUmNtlrmADJZs0sYjpWPCjqluV0wy0R1nNXBWI2d1HJBXqyqnHUzIecRvkfcrQkT4bv-oZifaKwydyAycOQTIU1ZkFtaxModvWth8wOETkGcoORoxPEoMEjrJ5nWtR5-O9FacgN-BQIX_I_ryuUf00hMVFbymyfzFDBgsxAbrUW70KEETmX7xUoq114S1_jtvA_J0VYw1MbqvdNW8pWHgR8P8Cci9TuhXg8MHIlKSi4CkvenQG71-STn52uKkg2fPYxE9OL9bT8jV4cHert4d7e88JNcYTlcM82QbZL2Zzd0jcDqb_HE70yk5vmjV8ge7Spbu |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Clinical+and+genetic+factors+associated+with+increased+risk+of+severe+liver+toxicity+in+a+monocentric+cohort+of+HIV+positive+patients+receiving+nevirapine-based+antiretroviral+therapy&rft.jtitle=BMC+infectious+diseases&rft.au=Giacomelli%2C+Andrea&rft.au=Riva%2C+Agostino&rft.au=Falvella%2C+Felicia+Stefania&rft.au=Oreni%2C+Maria+Letizia&rft.date=2018-11-12&rft.pub=BioMed+Central&rft.eissn=1471-2334&rft.volume=18&rft_id=info:doi/10.1186%2Fs12879-018-3462-5 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1471-2334&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1471-2334&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1471-2334&client=summon |