Influence of Liver Fibrosis Stage on Plasma Levels of Antiretroviral Drugs in HIV-Infected Patients with Chronic Hepatitis C
Background. Most antiretrovirals are metabolized in the liver, and lower dosing could be advisable in patients with severe liver insufficiency. Methods. Plasma drug levels were measured in hepatitis C virus (HCV)/human immunodeficiency virus (HIV)—coinfected patients receiving nevirapine (NVP), efav...
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| Veröffentlicht in: | The Journal of infectious diseases 2007-04, Vol.195 (7), p.973-979 |
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| creator | Barreiro, Pablo Rodríguez-Novoa, Sonia Labarga, Pablo Ruiz, Andrés Jiménez-Nácher, Inmaculada Martín-Carbonero, Luz Gonzalez-Lahoz, Juan Soriano, Vincent |
| description | Background. Most antiretrovirals are metabolized in the liver, and lower dosing could be advisable in patients with severe liver insufficiency. Methods. Plasma drug levels were measured in hepatitis C virus (HCV)/human immunodeficiency virus (HIV)—coinfected patients receiving nevirapine (NVP), efavirenz (EFV), lopinavir/ritonavir (LPV/r), or atazanavir (ATV) with or without ritonavir. Liver fibrosis was measured using elastometry. Results. A total of 268 coinfected patients with compensated liver disease were analyzed. Mean plasma levels were 6.1 μg/mL for NVP (35 patients), 2.8 μg/mL for EFV (46 patients), 5.8 μg/mL for LPV (56 patients), 0.4 μg/mL for ATV (58 patients), and 0.7 μg/mL for ATV/r (73 patients). Overall, drug levels were higher in patients with cirrhosis than in those without cirrhosis for EFV (median, 3.4 vs. 1.9 μg/mL; P< .01) and NVP (median, 6.6 vs. 5.8 μg/mL; P = .33). EFV plasma levels above the toxic threshold (>4 μg/mL) were more frequent in patients with cirrhosis than in those without (31% vs. 3%; P < .001). The same trend was seen for NVP levels >8 μg/mL (50% vs. 27%; P = .27). By contrast, plasma levels of protease inhibitors (PIs) did not differ significantly between patients with and those without cirrhosis. Conclusion. Liver clearance of nonnucleoside reverse-transcriptase inhibitors, particularly EFV, is impaired in patients with cirrhosis. No similar effect is seen for PIs. Assessment of liver fibrosis by noninvasive tools may identify HCV/HIV-coinfected patients who might benefit from therapeutic drug monitoring to avoid drug overexposure. |
| doi_str_mv | 10.1086/512086 |
| format | Article |
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Most antiretrovirals are metabolized in the liver, and lower dosing could be advisable in patients with severe liver insufficiency. Methods. Plasma drug levels were measured in hepatitis C virus (HCV)/human immunodeficiency virus (HIV)—coinfected patients receiving nevirapine (NVP), efavirenz (EFV), lopinavir/ritonavir (LPV/r), or atazanavir (ATV) with or without ritonavir. Liver fibrosis was measured using elastometry. Results. A total of 268 coinfected patients with compensated liver disease were analyzed. Mean plasma levels were 6.1 μg/mL for NVP (35 patients), 2.8 μg/mL for EFV (46 patients), 5.8 μg/mL for LPV (56 patients), 0.4 μg/mL for ATV (58 patients), and 0.7 μg/mL for ATV/r (73 patients). Overall, drug levels were higher in patients with cirrhosis than in those without cirrhosis for EFV (median, 3.4 vs. 1.9 μg/mL; P< .01) and NVP (median, 6.6 vs. 5.8 μg/mL; P = .33). EFV plasma levels above the toxic threshold (>4 μg/mL) were more frequent in patients with cirrhosis than in those without (31% vs. 3%; P < .001). The same trend was seen for NVP levels >8 μg/mL (50% vs. 27%; P = .27). By contrast, plasma levels of protease inhibitors (PIs) did not differ significantly between patients with and those without cirrhosis. Conclusion. Liver clearance of nonnucleoside reverse-transcriptase inhibitors, particularly EFV, is impaired in patients with cirrhosis. No similar effect is seen for PIs. Assessment of liver fibrosis by noninvasive tools may identify HCV/HIV-coinfected patients who might benefit from therapeutic drug monitoring to avoid drug overexposure.</description><identifier>ISSN: 0022-1899</identifier><identifier>EISSN: 1537-6613</identifier><identifier>DOI: 10.1086/512086</identifier><identifier>PMID: 17330787</identifier><identifier>CODEN: JIDIAQ</identifier><language>eng</language><publisher>Chicago, IL: The University of Chicago Press</publisher><subject><![CDATA[Adult ; AIDS ; Anti-HIV Agents - administration & dosage ; Anti-HIV Agents - blood ; Anti-HIV Agents - therapeutic use ; Antiretrovirals ; Antivirals ; Atazanavir Sulfate ; Benzoxazines ; Biological and medical sciences ; Blood plasma ; Chronic hepatitis ; Cirrhosis ; Drug Monitoring ; Female ; Fibrosis ; Fundamental and applied biological sciences. Psychology ; Hepatitis C virus ; Hepatitis C, Chronic - blood ; Hepatitis C, Chronic - pathology ; HIV Infections - drug therapy ; HIV/AIDS ; Human immunodeficiency virus ; Human viral diseases ; Humans ; Infectious diseases ; Liver ; Liver Cirrhosis - pathology ; Liver diseases ; Lopinavir ; Male ; Medical sciences ; Microbiology ; Nevirapine - administration & dosage ; Nevirapine - blood ; Nevirapine - therapeutic use ; Oligopeptides - administration & dosage ; Oligopeptides - blood ; Oligopeptides - therapeutic use ; Oxazines - administration & dosage ; Oxazines - blood ; Oxazines - therapeutic use ; Pharmacokinetics ; Pyridines - administration & dosage ; Pyridines - blood ; Pyridines - therapeutic use ; Pyrimidinones - administration & dosage ; Pyrimidinones - blood ; Pyrimidinones - therapeutic use ; Ritonavir - administration & dosage ; Ritonavir - blood ; Ritonavir - therapeutic use ; Severity of Illness Index ; Viral diseases ; Viral diseases of the lymphoid tissue and the blood. Aids ; Viral hepatitis]]></subject><ispartof>The Journal of infectious diseases, 2007-04, Vol.195 (7), p.973-979</ispartof><rights>Copyright 2007 Infectious Diseases Society of America</rights><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c430t-2c908598b60afa35535b9d3806972683d687eadf0d0913f686634354c417872f3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/30086028$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/30086028$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,780,784,803,27923,27924,58016,58249</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18621004$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17330787$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Barreiro, Pablo</creatorcontrib><creatorcontrib>Rodríguez-Novoa, Sonia</creatorcontrib><creatorcontrib>Labarga, Pablo</creatorcontrib><creatorcontrib>Ruiz, Andrés</creatorcontrib><creatorcontrib>Jiménez-Nácher, Inmaculada</creatorcontrib><creatorcontrib>Martín-Carbonero, Luz</creatorcontrib><creatorcontrib>Gonzalez-Lahoz, Juan</creatorcontrib><creatorcontrib>Soriano, Vincent</creatorcontrib><title>Influence of Liver Fibrosis Stage on Plasma Levels of Antiretroviral Drugs in HIV-Infected Patients with Chronic Hepatitis C</title><title>The Journal of infectious diseases</title><addtitle>The Journal of Infectious Diseases</addtitle><description>Background. Most antiretrovirals are metabolized in the liver, and lower dosing could be advisable in patients with severe liver insufficiency. Methods. Plasma drug levels were measured in hepatitis C virus (HCV)/human immunodeficiency virus (HIV)—coinfected patients receiving nevirapine (NVP), efavirenz (EFV), lopinavir/ritonavir (LPV/r), or atazanavir (ATV) with or without ritonavir. Liver fibrosis was measured using elastometry. Results. A total of 268 coinfected patients with compensated liver disease were analyzed. Mean plasma levels were 6.1 μg/mL for NVP (35 patients), 2.8 μg/mL for EFV (46 patients), 5.8 μg/mL for LPV (56 patients), 0.4 μg/mL for ATV (58 patients), and 0.7 μg/mL for ATV/r (73 patients). Overall, drug levels were higher in patients with cirrhosis than in those without cirrhosis for EFV (median, 3.4 vs. 1.9 μg/mL; P< .01) and NVP (median, 6.6 vs. 5.8 μg/mL; P = .33). EFV plasma levels above the toxic threshold (>4 μg/mL) were more frequent in patients with cirrhosis than in those without (31% vs. 3%; P < .001). The same trend was seen for NVP levels >8 μg/mL (50% vs. 27%; P = .27). By contrast, plasma levels of protease inhibitors (PIs) did not differ significantly between patients with and those without cirrhosis. Conclusion. Liver clearance of nonnucleoside reverse-transcriptase inhibitors, particularly EFV, is impaired in patients with cirrhosis. No similar effect is seen for PIs. Assessment of liver fibrosis by noninvasive tools may identify HCV/HIV-coinfected patients who might benefit from therapeutic drug monitoring to avoid drug overexposure.</description><subject>Adult</subject><subject>AIDS</subject><subject>Anti-HIV Agents - administration & dosage</subject><subject>Anti-HIV Agents - blood</subject><subject>Anti-HIV Agents - therapeutic use</subject><subject>Antiretrovirals</subject><subject>Antivirals</subject><subject>Atazanavir Sulfate</subject><subject>Benzoxazines</subject><subject>Biological and medical sciences</subject><subject>Blood plasma</subject><subject>Chronic hepatitis</subject><subject>Cirrhosis</subject><subject>Drug Monitoring</subject><subject>Female</subject><subject>Fibrosis</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Hepatitis C virus</subject><subject>Hepatitis C, Chronic - blood</subject><subject>Hepatitis C, Chronic - pathology</subject><subject>HIV Infections - drug therapy</subject><subject>HIV/AIDS</subject><subject>Human immunodeficiency virus</subject><subject>Human viral diseases</subject><subject>Humans</subject><subject>Infectious diseases</subject><subject>Liver</subject><subject>Liver Cirrhosis - pathology</subject><subject>Liver diseases</subject><subject>Lopinavir</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Microbiology</subject><subject>Nevirapine - administration & dosage</subject><subject>Nevirapine - blood</subject><subject>Nevirapine - therapeutic use</subject><subject>Oligopeptides - administration & dosage</subject><subject>Oligopeptides - blood</subject><subject>Oligopeptides - therapeutic use</subject><subject>Oxazines - administration & dosage</subject><subject>Oxazines - blood</subject><subject>Oxazines - therapeutic use</subject><subject>Pharmacokinetics</subject><subject>Pyridines - administration & dosage</subject><subject>Pyridines - blood</subject><subject>Pyridines - therapeutic use</subject><subject>Pyrimidinones - administration & dosage</subject><subject>Pyrimidinones - blood</subject><subject>Pyrimidinones - therapeutic use</subject><subject>Ritonavir - administration & dosage</subject><subject>Ritonavir - blood</subject><subject>Ritonavir - therapeutic use</subject><subject>Severity of Illness Index</subject><subject>Viral diseases</subject><subject>Viral diseases of the lymphoid tissue and the blood. Aids</subject><subject>Viral hepatitis</subject><issn>0022-1899</issn><issn>1537-6613</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkV9r2zAUxcVYWbNs-wYbetne3Eq6tiQ_lmytA4YG9ofRF6HIUqvOsVNJzjbYh59CQvN04Zwf53LPRegdJReUSH5ZUZbHCzSjFYiCcwov0YwQxgoq6_ocvY7xkRBSAhev0DkVAERIMUP_loPrJzsYi0eHW7-zAV_7dRijj_hr0vdZH_Cq13GjcWt3to978GpIPtgUxp0Pusefw3QfsR9ws_xR5ERrku3wSidvhxTxb58e8OIhjIM3uLHbrKccv3iDzpzuo317nHP0_frLt0VTtLc3y8VVW5gSSCqYqYmsarnmRDsNVQXVuu5AEl4LxiV0XAqrO0c6UlNwXHIOJVSlKWm-kTmYo0-H3G0YnyYbk9r4aGzf68GOU1S05kB5yU6gyQXEYJ3aBr_R4a-iRO17VoeeM_jhmDitN7Y7YcdiM_DxCOhodO-CHoyPJ05yRvfvmKP3B-4xpjE8-0DyFsJk9ouD72Oyf559HX4pLkBUqvl5pzhf3TX8ZqVa-A_arptx</recordid><startdate>20070401</startdate><enddate>20070401</enddate><creator>Barreiro, Pablo</creator><creator>Rodríguez-Novoa, Sonia</creator><creator>Labarga, Pablo</creator><creator>Ruiz, Andrés</creator><creator>Jiménez-Nácher, Inmaculada</creator><creator>Martín-Carbonero, Luz</creator><creator>Gonzalez-Lahoz, Juan</creator><creator>Soriano, Vincent</creator><general>The University of Chicago Press</general><general>University of Chicago Press</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7U9</scope><scope>H94</scope></search><sort><creationdate>20070401</creationdate><title>Influence of Liver Fibrosis Stage on Plasma Levels of Antiretroviral Drugs in HIV-Infected Patients with Chronic Hepatitis C</title><author>Barreiro, Pablo ; Rodríguez-Novoa, Sonia ; Labarga, Pablo ; Ruiz, Andrés ; Jiménez-Nácher, Inmaculada ; Martín-Carbonero, Luz ; Gonzalez-Lahoz, Juan ; Soriano, Vincent</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c430t-2c908598b60afa35535b9d3806972683d687eadf0d0913f686634354c417872f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Adult</topic><topic>AIDS</topic><topic>Anti-HIV Agents - administration & dosage</topic><topic>Anti-HIV Agents - blood</topic><topic>Anti-HIV Agents - therapeutic use</topic><topic>Antiretrovirals</topic><topic>Antivirals</topic><topic>Atazanavir Sulfate</topic><topic>Benzoxazines</topic><topic>Biological and medical sciences</topic><topic>Blood plasma</topic><topic>Chronic hepatitis</topic><topic>Cirrhosis</topic><topic>Drug Monitoring</topic><topic>Female</topic><topic>Fibrosis</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Hepatitis C virus</topic><topic>Hepatitis C, Chronic - blood</topic><topic>Hepatitis C, Chronic - pathology</topic><topic>HIV Infections - drug therapy</topic><topic>HIV/AIDS</topic><topic>Human immunodeficiency virus</topic><topic>Human viral diseases</topic><topic>Humans</topic><topic>Infectious diseases</topic><topic>Liver</topic><topic>Liver Cirrhosis - pathology</topic><topic>Liver diseases</topic><topic>Lopinavir</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Microbiology</topic><topic>Nevirapine - administration & dosage</topic><topic>Nevirapine - blood</topic><topic>Nevirapine - therapeutic use</topic><topic>Oligopeptides - administration & dosage</topic><topic>Oligopeptides - blood</topic><topic>Oligopeptides - therapeutic use</topic><topic>Oxazines - administration & dosage</topic><topic>Oxazines - blood</topic><topic>Oxazines - therapeutic use</topic><topic>Pharmacokinetics</topic><topic>Pyridines - administration & dosage</topic><topic>Pyridines - blood</topic><topic>Pyridines - therapeutic use</topic><topic>Pyrimidinones - administration & dosage</topic><topic>Pyrimidinones - blood</topic><topic>Pyrimidinones - therapeutic use</topic><topic>Ritonavir - administration & dosage</topic><topic>Ritonavir - blood</topic><topic>Ritonavir - therapeutic use</topic><topic>Severity of Illness Index</topic><topic>Viral diseases</topic><topic>Viral diseases of the lymphoid tissue and the blood. Aids</topic><topic>Viral hepatitis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Barreiro, Pablo</creatorcontrib><creatorcontrib>Rodríguez-Novoa, Sonia</creatorcontrib><creatorcontrib>Labarga, Pablo</creatorcontrib><creatorcontrib>Ruiz, Andrés</creatorcontrib><creatorcontrib>Jiménez-Nácher, Inmaculada</creatorcontrib><creatorcontrib>Martín-Carbonero, Luz</creatorcontrib><creatorcontrib>Gonzalez-Lahoz, Juan</creatorcontrib><creatorcontrib>Soriano, Vincent</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>The Journal of infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Barreiro, Pablo</au><au>Rodríguez-Novoa, Sonia</au><au>Labarga, Pablo</au><au>Ruiz, Andrés</au><au>Jiménez-Nácher, Inmaculada</au><au>Martín-Carbonero, Luz</au><au>Gonzalez-Lahoz, Juan</au><au>Soriano, Vincent</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Influence of Liver Fibrosis Stage on Plasma Levels of Antiretroviral Drugs in HIV-Infected Patients with Chronic Hepatitis C</atitle><jtitle>The Journal of infectious diseases</jtitle><addtitle>The Journal of Infectious Diseases</addtitle><date>2007-04-01</date><risdate>2007</risdate><volume>195</volume><issue>7</issue><spage>973</spage><epage>979</epage><pages>973-979</pages><issn>0022-1899</issn><eissn>1537-6613</eissn><coden>JIDIAQ</coden><abstract>Background. Most antiretrovirals are metabolized in the liver, and lower dosing could be advisable in patients with severe liver insufficiency. Methods. Plasma drug levels were measured in hepatitis C virus (HCV)/human immunodeficiency virus (HIV)—coinfected patients receiving nevirapine (NVP), efavirenz (EFV), lopinavir/ritonavir (LPV/r), or atazanavir (ATV) with or without ritonavir. Liver fibrosis was measured using elastometry. Results. A total of 268 coinfected patients with compensated liver disease were analyzed. Mean plasma levels were 6.1 μg/mL for NVP (35 patients), 2.8 μg/mL for EFV (46 patients), 5.8 μg/mL for LPV (56 patients), 0.4 μg/mL for ATV (58 patients), and 0.7 μg/mL for ATV/r (73 patients). Overall, drug levels were higher in patients with cirrhosis than in those without cirrhosis for EFV (median, 3.4 vs. 1.9 μg/mL; P< .01) and NVP (median, 6.6 vs. 5.8 μg/mL; P = .33). EFV plasma levels above the toxic threshold (>4 μg/mL) were more frequent in patients with cirrhosis than in those without (31% vs. 3%; P < .001). The same trend was seen for NVP levels >8 μg/mL (50% vs. 27%; P = .27). By contrast, plasma levels of protease inhibitors (PIs) did not differ significantly between patients with and those without cirrhosis. Conclusion. Liver clearance of nonnucleoside reverse-transcriptase inhibitors, particularly EFV, is impaired in patients with cirrhosis. No similar effect is seen for PIs. Assessment of liver fibrosis by noninvasive tools may identify HCV/HIV-coinfected patients who might benefit from therapeutic drug monitoring to avoid drug overexposure.</abstract><cop>Chicago, IL</cop><pub>The University of Chicago Press</pub><pmid>17330787</pmid><doi>10.1086/512086</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | The Journal of infectious diseases, 2007-04, Vol.195 (7), p.973-979 |
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| language | eng |
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| source | MEDLINE; JSTOR Archive Collection A-Z Listing; Oxford University Press Journals All Titles (1996-Current); Alma/SFX Local Collection |
| subjects | Adult AIDS Anti-HIV Agents - administration & dosage Anti-HIV Agents - blood Anti-HIV Agents - therapeutic use Antiretrovirals Antivirals Atazanavir Sulfate Benzoxazines Biological and medical sciences Blood plasma Chronic hepatitis Cirrhosis Drug Monitoring Female Fibrosis Fundamental and applied biological sciences. Psychology Hepatitis C virus Hepatitis C, Chronic - blood Hepatitis C, Chronic - pathology HIV Infections - drug therapy HIV/AIDS Human immunodeficiency virus Human viral diseases Humans Infectious diseases Liver Liver Cirrhosis - pathology Liver diseases Lopinavir Male Medical sciences Microbiology Nevirapine - administration & dosage Nevirapine - blood Nevirapine - therapeutic use Oligopeptides - administration & dosage Oligopeptides - blood Oligopeptides - therapeutic use Oxazines - administration & dosage Oxazines - blood Oxazines - therapeutic use Pharmacokinetics Pyridines - administration & dosage Pyridines - blood Pyridines - therapeutic use Pyrimidinones - administration & dosage Pyrimidinones - blood Pyrimidinones - therapeutic use Ritonavir - administration & dosage Ritonavir - blood Ritonavir - therapeutic use Severity of Illness Index Viral diseases Viral diseases of the lymphoid tissue and the blood. Aids Viral hepatitis |
| title | Influence of Liver Fibrosis Stage on Plasma Levels of Antiretroviral Drugs in HIV-Infected Patients with Chronic Hepatitis C |
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