Pharmacogenetics and Clinical Biomarkers for Subtherapeutic Plasma Efavirenz Concentration in HIV-1 Infected Thai Adults
The aim of this study was to assess the influence of host genetic variations and clinical factors in relation to efavirenz level in HIV-1 infected Thai adults. A total of 100 HIV-infected subjects treated with efavirenz/lamivudine/tenofivir were prospectively enrolled. The panel of CYP2A6, CYP2B6 an...
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| Published in | DRUG METABOLISM AND PHARMACOKINETICS Vol. 29; no. 4; pp. 289 - 295 |
|---|---|
| Main Authors | , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
England
Elsevier Ltd
2014
Japanese Society for the Study of Xenobiotics |
| Subjects | |
| Online Access | Get full text |
| ISSN | 1347-4367 1880-0920 1880-0920 |
| DOI | 10.2133/dmpk.DMPK-13-RG-077 |
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| Abstract | The aim of this study was to assess the influence of host genetic variations and clinical factors in relation to efavirenz level in HIV-1 infected Thai adults. A total of 100 HIV-infected subjects treated with efavirenz/lamivudine/tenofivir were prospectively enrolled. The panel of CYP2A6, CYP2B6 and CYP3A4/5 polymorphisms was genotyped. At steady state, plasma efavirenz concentrations were measured using high performance liquid chromatography. The relationship between host genetic and clinical factors in terms of efavirenz pharmacokinetics in HIV-1 infected Thai adults was analyzed. The minor allele frequency for CYP2A6 –48T>G, CYP2B6 g.18492T>C, CYP3A4*1B c.–392A>G, CYP3A4*18 c.878T>C and CYP3A5*3 c.6986A>G was 0.14, 0.27, 0.01, 0.03 and 0.38, respectively. Univariant and multivariant analysis indicated associations for CYP2B6 g.18492T>C (p < 0.001 and p = 0.001), aspartate aminotransferase (AST; p = 0.001 and p = 0.006) and blood urea nitrogen (BUN; p = 0.011 and p = 0.016) with plasma efavirenz concentration. However, CYP2A6 –48T>G, CYP3A4*1B c.–392A>G, CYP3A4*18 c.878T>C and CYP3A5*3 c.6986A>G had no significant impact on plasma efavirenz concentration in HIV-1 infected Thai adults. The CYP2B6 g.18492T>C polymorphism, AST and BUN were significantly associated with low efavirenz concentrations. The results from this study can be used to improve the prediction of efavirenz plasma concentration and to optimize its dose in antiretroviral therapy. |
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| AbstractList | The aim of this study was to assess the influence of host genetic variations and clinical factors in relation to efavirenz level in HIV-1 infected Thai adults. A total of 100 HIV-infected subjects treated with efavirenz/lamivudine/tenofivir were prospectively enrolled. The panel of CYP2A6, CYP2B6 and CYP3A4/5 polymorphisms was genotyped. At steady state, plasma efavirenz concentrations were measured using high performance liquid chromatography. The relationship between host genetic and clinical factors in terms of efavirenz pharmacokinetics in HIV-1 infected Thai adults was analyzed. The minor allele frequency for CYP2A6 -48T>G, CYP2B6 g.18492T>C, CYP3A4*1B c.-392A>G, CYP3A4*18 c.878T>C and CYP3A5*3 c.6986A>G was 0.14, 0.27, 0.01, 0.03 and 0.38, respectively. Univariant and multivariant analysis indicated associations for CYP2B6 g.18492T>C (p < 0.001 and p = 0.001), aspartate aminotransferase (AST; p = 0.001 and p = 0.006) and blood urea nitrogen (BUN; p = 0.011 and p = 0.016) with plasma efavirenz concentration. However, CYP2A6 -48T>G, CYP3A4*1B c.-392A>G, CYP3A4*18 c.878T>C and CYP3A5*3 c.6986A>G had no significant impact on plasma efavirenz concentration in HIV-1 infected Thai adults. The CYP2B6 g.18492T>C polymorphism, AST and BUN were significantly associated with low efavirenz concentrations. The results from this study can be used to improve the prediction of efavirenz plasma concentration and to optimize its dose in antiretroviral therapy. [Summary]: The aim of this study was to assess the influence of host genetic variations and clinical factors in relation to efavirenz level in HIV-1 infected Thai adults. A total of 100 HIV-infected subjects treated with efavirenz/lamivudine/tenofivir were prospectively enrolled. The panel of CYP2A6, CYP2B6 and CYP3A4/5 polymorphisms was genotyped. At steady state, plasma efavirenz concentrations were measured using high performance liquid chromatography. The relationship between host genetic and clinical factors in terms of efavirenz pharmacokinetics in HIV-1 infected Thai adults was analyzed. The minor allele frequency for CYP2A6 -48T>G, CYP2B6 g. 18492T>C, CYP3A4*1B c. -392A>G, CYP3A4*18 c. 878T>C and CYP3A5*3 c. 6986A>G was 0.14, 0.27, 0.01, 0.03 and 0.38, respectively. Univariant and multivariant analysis indicated associations for CYP2B6 g. 18492T>C (p < 0.001 and p = 0.001), aspartate aminotransferase (AST; p = 0.001 and p = 0.006) and blood urea nitrogen (BUN; p = 0.011 and p = 0.016) with plasma efavirenz concentration. However, CYP2A6 -48T>G, CYP3A4*1B c. -392A>G, CYP3A4*18 c. 878T>C and CYP3A5*3 c. 6986A>G had no significant impact on plasma efavirenz concentration in HIV-1 infected Thai adults. The CYP2B6 g. 18492T>C polymorphism, AST and BUN were significantly associated with low efavirenz concentrations. The results from this study can be used to improve the prediction of efavirenz plasma concentration and to optimize its dose in antiretroviral therapy. The aim of this study was to assess the influence of host genetic variations and clinical factors in relation to efavirenz level in HIV-1 infected Thai adults. A total of 100 HIV-infected subjects treated with efavirenz/lamivudine/tenofivir were prospectively enrolled. The panel of CYP2A6, CYP2B6 and CYP3A4/5 polymorphisms was genotyped. At steady state, plasma efavirenz concentrations were measured using high performance liquid chromatography. The relationship between host genetic and clinical factors in terms of efavirenz pharmacokinetics in HIV-1 infected Thai adults was analyzed. The minor allele frequency for CYP2A6 -48T>G, CYP2B6 g.18492T>C, CYP3A4*1B c.-392A>G, CYP3A4*18 c.878T>C and CYP3A5*3 c.6986A>G was 0.14, 0.27, 0.01, 0.03 and 0.38, respectively. Univariant and multivariant analysis indicated associations for CYP2B6 g.18492T>C (p < 0.001 and p = 0.001), aspartate aminotransferase (AST; p = 0.001 and p = 0.006) and blood urea nitrogen (BUN; p = 0.011 and p = 0.016) with plasma efavirenz concentration. However, CYP2A6 -48T>G, CYP3A4*1B c.-392A>G, CYP3A4*18 c.878T>C and CYP3A5*3 c.6986A>G had no significant impact on plasma efavirenz concentration in HIV-1 infected Thai adults. The CYP2B6 g.18492T>C polymorphism, AST and BUN were significantly associated with low efavirenz concentrations. The results from this study can be used to improve the prediction of efavirenz plasma concentration and to optimize its dose in antiretroviral therapy.The aim of this study was to assess the influence of host genetic variations and clinical factors in relation to efavirenz level in HIV-1 infected Thai adults. A total of 100 HIV-infected subjects treated with efavirenz/lamivudine/tenofivir were prospectively enrolled. The panel of CYP2A6, CYP2B6 and CYP3A4/5 polymorphisms was genotyped. At steady state, plasma efavirenz concentrations were measured using high performance liquid chromatography. The relationship between host genetic and clinical factors in terms of efavirenz pharmacokinetics in HIV-1 infected Thai adults was analyzed. The minor allele frequency for CYP2A6 -48T>G, CYP2B6 g.18492T>C, CYP3A4*1B c.-392A>G, CYP3A4*18 c.878T>C and CYP3A5*3 c.6986A>G was 0.14, 0.27, 0.01, 0.03 and 0.38, respectively. Univariant and multivariant analysis indicated associations for CYP2B6 g.18492T>C (p < 0.001 and p = 0.001), aspartate aminotransferase (AST; p = 0.001 and p = 0.006) and blood urea nitrogen (BUN; p = 0.011 and p = 0.016) with plasma efavirenz concentration. However, CYP2A6 -48T>G, CYP3A4*1B c.-392A>G, CYP3A4*18 c.878T>C and CYP3A5*3 c.6986A>G had no significant impact on plasma efavirenz concentration in HIV-1 infected Thai adults. The CYP2B6 g.18492T>C polymorphism, AST and BUN were significantly associated with low efavirenz concentrations. The results from this study can be used to improve the prediction of efavirenz plasma concentration and to optimize its dose in antiretroviral therapy. |
| Author | Santon, Siwalee Koomdee, Napatrupron Prommas, Santirat Chamnanphon, Montri Manosuthi, Weerawat Jantararoungtong, Thawinee Sukasem, Chonlaphat Puangpetch, Apichaya |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/24477223$$D View this record in MEDLINE/PubMed |
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| CitedBy_id | crossref_primary_10_1093_jac_dkz329 crossref_primary_10_1002_cpt_1477 crossref_primary_10_2217_pgs_2016_0097 crossref_primary_10_1016_j_dmpk_2021_100399 crossref_primary_10_1097_AOG_0000000000003189 crossref_primary_10_1080_09540121_2022_2067518 crossref_primary_10_2217_pgs_2017_0009 crossref_primary_10_1097_FPC_0000000000000145 crossref_primary_10_2217_pme_15_54 crossref_primary_10_3390_jpm7040018 crossref_primary_10_1038_s41397_018_0028_2 crossref_primary_10_1016_j_meegid_2015_11_014 crossref_primary_10_2147_PGPM_S306358 |
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| Keywords | CYP3A4/5 clinical factors CYP2A6 CYP2B6 subtherapeutic level efavirenz |
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| Snippet | The aim of this study was to assess the influence of host genetic variations and clinical factors in relation to efavirenz level in HIV-1 infected Thai adults.... [Summary]: The aim of this study was to assess the influence of host genetic variations and clinical factors in relation to efavirenz level in HIV-1 infected... |
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| SubjectTerms | Adenine - analogs & derivatives Adenine - therapeutic use Adolescent Adult Anti-HIV Agents - blood Anti-HIV Agents - therapeutic use Asian Continental Ancestry Group - genetics Benzoxazines - blood Benzoxazines - therapeutic use Biomarkers clinical factors CYP2A6 CYP2B6 CYP3A4/5 Cytochrome P-450 Enzyme System - genetics efavirenz Female Gene Frequency HIV Infections - blood HIV Infections - drug therapy HIV Infections - genetics Humans Lamivudine - therapeutic use Male Organophosphonates - therapeutic use Polymorphism, Single Nucleotide - genetics Prospective Studies subtherapeutic level Tenofovir Young Adult |
| Title | Pharmacogenetics and Clinical Biomarkers for Subtherapeutic Plasma Efavirenz Concentration in HIV-1 Infected Thai Adults |
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