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Antiretroviral treatment exposure was categorized as follows: no exposure and ongoing short- and long-term exposure (&amp;lt;2 or \u22652 years) after initiation. Association between development of cLEE and ART exposure was investigated using Poisson regression.<\/jats:p><jats:p>Results. \u2003Among 21 485 participants observed for 105 413 person-years (PY), 6368 developed cLEE (incidence 6.04\/100 PY; 95% confidence interval [CI], 5.89\u20136.19). Chronic liver enzyme elevation was associated with short-and long-term exposure to didanosine (&amp;lt;2 years rate ratio [RR] = 1.29, 95% CI, 1.11\u20131.49; &amp;gt;2 years RR = 1.26, 95% CI, 1.13\u20131.41); stavudine (&amp;lt;2 years RR = 1.51, 95% CI, 1.26\u20131.81; &amp;gt;2 years RR = 1.17, 95% CI, 1.03\u20131.32), and tenofovir disoproxil fumarate (&amp;lt;2 years RR = 1.55, 95% CI, 1.40\u20131.72; &amp;gt;2 years RR = 1.18, 95% CI, 1.05\u20131.32), but only short-term exposure to nevirapine (&amp;lt;2 years RR = 1.44, 95% CI, 1.29\u20131.61), efavirenz (&amp;lt;2 years RR = 1.14, 95% CI, 1.03\u20131.26), emtricitabine (&amp;lt;2 years RR = 1.18, 95% CI, 1.04\u20131.33), and atazanavir (&amp;lt;2 years RR = 1.20, 95% CI, 1.04\u20131.38). Chronic liver enzyme elevation was not associated with use of lamivudine, abacavir, and other protease inhibitors. Mortality did not differ between participants with and without cLEE.<\/jats:p><jats:p>Conclusions. \u2003Although didanosine, stavudine, nevirapine, and efavirenz have been described to be hepatotoxic, we additionally observed a consistent association between tenofovir and cLEE emerging within the first 2 years after drug initiation. This novel tenofovir-cLEE signal should be further investigated.<\/jats:p>","DOI":"10.1093\/ofid\/ofw009","type":"journal-article","created":{"date-parts":[[2016,2,26]],"date-time":"2016-02-26T02:11:24Z","timestamp":1456452684000},"source":"Crossref","is-referenced-by-count":22,"title":["Antiretroviral Drugs and Risk of Chronic Alanine Aminotransferase Elevation in Human Immunodeficiency Virus (HIV)-Monoinfected Persons: The Data Collection on Adverse Events of Anti-HIV Drugs Study"],"prefix":"10.1093","volume":"3","author":[{"given":"Helen","family":"Kovari","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline A.","family":"Sabin","sequence":"additional","affiliation":[{"name":"Research Department of Infection and Population Health, University College London, United 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