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Separate marginal structural models were used to estimate hazard ratios (HRs) of each outcome associated with cumulative exposure to ART regimens that contain mtNRTIs versus regimens that contain other NRTIs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Over 7033 person\u2010years, we observed 97 (5.6%) decompensation events (incidence rate, 13.8\/1000 person\u2010years) and 125 (7.2%) deaths (incidence rate, 17.8 events\/1000 person\u2010years). The risk of hepatic decompensation increased with cumulative mtNRTI use (1\u201011\u00a0mo: HR, 1.79 [95% confidence interval (CI), 0.74\u20104.31]; 12\u201035\u00a0mo: HR, 1.39 [95% CI, 0.68\u20102.87]; 36\u201071\u00a0mo: HR, 2.27 [95% CI, 0.92\u20105.60]; &gt;71\u00a0mo: HR, 4.66 [95% CI, 1.04\u201020.83];<jats:italic>P<\/jats:italic>\u00a0=\u00a0.045) versus nonuse. Cumulative mtNRTI use also increased risk of death (1\u201011\u00a0mo: HR, 2.24 [95% CI, 1.04\u20104.81]; 12\u201035\u00a0mo: HR, 2.05 [95% CI, 0.68\u20106.20]; 36\u201071\u00a0mo: HR, 3.04 [95% CI, 1.12\u20108.26]; &gt;71\u00a0mo: HR, 3.93 [95% CI, 0.75\u201020.50];<jats:italic>P<\/jats:italic>\u00a0=\u00a0.030).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings suggest that cumulative mtNRTI use may increase the risk of hepatic decompensation and death in HIV\/HCV coinfection. These drugs should be avoided when alternatives exist for HIV\/HCV patients.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pds.4258","type":"journal-article","created":{"date-parts":[[2017,7,19]],"date-time":"2017-07-19T11:55:27Z","timestamp":1500465327000},"page":"1172-1181","source":"Crossref","is-referenced-by-count":9,"title":["Risk of liver decompensation with cumulative use of mitochondrial toxic nucleoside analogues in HIV\/hepatitis C virus coinfection"],"prefix":"10.1002","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7955-0600","authenticated-orcid":false,"suffix":"3rd","given":"Vincent","family":"Lo Re","sequence":"first","affiliation":[{"name":"Department of Medicine, Perelman School of Medicine University of Pennsylvania Philadelphia PA USA"},{"name":"Department of Biostatistics and Epidemiology, Center for Clinical Epidemiology and Biostatistics, and Center for Pharmacoepidemiology Research and Training, Perelman School of Medicine University of Pennsylvania Philadelphia PA USA"},{"name":"Medical Service, Corporal Michael J. 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