{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T12:35:50Z","timestamp":1751459750556},"reference-count":15,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2012,3,14]],"date-time":"2012-03-14T00:00:00Z","timestamp":1331683200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["HIV Medicine"],"published-print":{"date-parts":[[2012,8]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>The aim of this study was to assess the incidence of hepatotoxicity in patients who had used nonnucleoside reverse transcriptase inhibitors (<jats:styled-content style=\"fixed-case\">NNRTIs<\/jats:styled-content>) for at least 3 years.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The study group consisted of <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content>\u2010infected patients under follow\u2010up at our clinic, who had continuously used an <jats:styled-content style=\"fixed-case\">NNRTI<\/jats:styled-content>\u2010containing regimen (efavirenz or nevirapine) for at least 3 years. Patients who had used protease inhibitors (<jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>s) for the same time span constituted a control group. Hepatotoxicity was graded according to the modified <jats:styled-content style=\"fixed-case\">AIDS C<\/jats:styled-content>linical <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>rial <jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>roup grading system, using alanine aminotransferase (<jats:styled-content style=\"fixed-case\">ALT<\/jats:styled-content>) as a marker.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>One hundred and twenty\u2010two patients on an <jats:styled-content style=\"fixed-case\">NNRTI<\/jats:styled-content> regimen and 54 <jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>\u2010using patients were included in the analysis. The mean follow\u2010up time was nearly 6 years. Eighteen <jats:styled-content style=\"fixed-case\">NNRTI<\/jats:styled-content>\u2010using patients (14.8%) developed a clinically relevant (\u2265\u2009grade <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content>) event of hepatotoxicity during treatment; five of them (4.1%) developed severe hepatotoxicity (\u2265\u2009grade <jats:styled-content style=\"fixed-case\">III<\/jats:styled-content>). No significant difference in the hepatotoxicity rate was seen between <jats:styled-content style=\"fixed-case\">NNRTI<\/jats:styled-content>\u2010 and <jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>\u2010using patients (14.8 <jats:italic>vs.<\/jats:italic> 18.5%, respectively; <jats:italic><jats:styled-content style=\"fixed-case\">P<\/jats:styled-content><\/jats:italic>\u2009=\u20090.52) or between patients using efavirenz and nevirapine (13.8% <jats:italic>vs.<\/jats:italic> 16.7%, respectively; <jats:italic><jats:styled-content style=\"fixed-case\">P<\/jats:styled-content><\/jats:italic>\u2009=\u20090.51). A hepatitis <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content> virus (<jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>) coinfection was associated with an increased risk of the development of hepatotoxicity during <jats:styled-content style=\"fixed-case\">NNRTI<\/jats:styled-content> therapy [odds ratio (<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>) 1.83; 95% confidence interval (<jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>) 1.33\u20134.24; <jats:italic><jats:styled-content style=\"fixed-case\">P<\/jats:styled-content><\/jats:italic>\u2009&lt;\u20090.01]. Finally, we observed that more hepatotoxic events occurred during the first year of <jats:styled-content style=\"fixed-case\">NNRTI<\/jats:styled-content> therapy compared with the entire period after 1 year (6.6 <jats:italic>vs.<\/jats:italic> 2.8 events, respectively, per 100 person\u2010years of treatment; <jats:italic><jats:styled-content style=\"fixed-case\">P<\/jats:styled-content><\/jats:italic>\u2009=\u20090.04).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Long\u2010term <jats:styled-content style=\"fixed-case\">NNRTI<\/jats:styled-content> use was not associated with a higher risk of clinically significant liver toxicity in patients who had been treated with <jats:styled-content style=\"fixed-case\">NNRTI<\/jats:styled-content> for at least 3 years.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1468-1293.2012.00995.x","type":"journal-article","created":{"date-parts":[[2012,3,14]],"date-time":"2012-03-14T04:21:42Z","timestamp":1331698902000},"page":"448-452","source":"Crossref","is-referenced-by-count":9,"title":["No increased risk of hepatotoxicity in long\u2010term use of nonnucleoside reverse transcriptase inhibitors in <scp>HIV<\/scp>\u2010infected patients"],"prefix":"10.1111","volume":"13","author":[{"given":"BJ","family":"Van Welzen","sequence":"first","affiliation":[{"name":"Department of Internal Medicine and Infectious Diseases University Medical Center Utrecht  Utrecht the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T","family":"Mudrikova","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Infectious Diseases University Medical Center Utrecht  Utrecht the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JE","family":"Arends","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Infectious Diseases University Medical Center Utrecht  Utrecht the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"AIM","family":"Hoepelman","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Infectious Diseases University Medical Center Utrecht  Utrecht the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,3,14]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2002.30319"},{"key":"e_1_2_5_3_1","first-page":"343","article-title":"Hepatotoxicity in patients prescribed efavirenz or nevirapine","volume":"13","author":"Br\u00fcck S","year":"2008","journal-title":"Eur J Med 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