{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T16:04:46Z","timestamp":1785168286646,"version":"3.55.0"},"reference-count":34,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2016,9,21]],"date-time":"2016-09-21T00:00:00Z","timestamp":1474416000000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:p>Direct\u2010acting antivirals (<jats:styled-content style=\"fixed-case\">DAA<\/jats:styled-content>s) have revolutionized the treatment of hepatitis C virus (<jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>) infection, with superior efficacy and safety compared to interferon\u2010based therapies. Despite these improvements, drug interactions with <jats:styled-content style=\"fixed-case\">DAA<\/jats:styled-content>s exist and may be clinically relevant in human immunodeficiency virus (<jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content>)\u2010coinfected patients. We present a case of nephrotoxicity associated with concomitant use of tenofovir disoproxil fumarate (<jats:styled-content style=\"fixed-case\">TDF<\/jats:styled-content>) and ledipasvir\u2010sofosbuvir (<jats:styled-content style=\"fixed-case\">LDV<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">SOF<\/jats:styled-content>). A 56\u2010year\u2010old woman with <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content> infection who had been taking efavirenz\/tenofovir\/emtricitabine (<jats:styled-content style=\"fixed-case\">EFV<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">TDF<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">FTC<\/jats:styled-content>) for 6\u00a0years developed acute kidney injury 8\u00a0weeks after initiating <jats:styled-content style=\"fixed-case\">LDV<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">SOF<\/jats:styled-content> for the treatment of <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> infection. Her serum creatinine concentration peaked at 10\u00a0mg\/<jats:styled-content style=\"fixed-case\">dL<\/jats:styled-content>, compared with her baseline concentration of 0.9\u20131\u00a0mg\/<jats:styled-content style=\"fixed-case\">dL<\/jats:styled-content>. Kidney biopsy revealed acute tubular necrosis and acute interstitial nephritis. Both <jats:styled-content style=\"fixed-case\">LDV<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">SOF<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">TDF<\/jats:styled-content> were discontinued, and the patient's serum creatinine concentration decreased to 1.3\u00a0mg\/<jats:styled-content style=\"fixed-case\">dL<\/jats:styled-content> over the following 6\u00a0weeks. We postulate that this adverse drug reaction may have been secondary to the known interaction between ledipasvir and <jats:styled-content style=\"fixed-case\">TDF<\/jats:styled-content>, which results in increased <jats:styled-content style=\"fixed-case\">TDF<\/jats:styled-content> exposure. Despite knowledge of this interaction, <jats:styled-content style=\"fixed-case\">LDV<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">SOF<\/jats:styled-content> is commonly prescribed in patients with <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> coinfection, as patients who received <jats:styled-content style=\"fixed-case\">LDV<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">SOF<\/jats:styled-content>\u2013 and <jats:styled-content style=\"fixed-case\">TDF<\/jats:styled-content>\u2010containing regimens in trials have not demonstrated adverse clinical consequences related to this interaction. This case highlights the rare but potentially serious nephrotoxicity that can result from <jats:styled-content style=\"fixed-case\">TDF<\/jats:styled-content> toxicity and serves as a reminder to clinicians to implement close renal function monitoring in patients receiving both <jats:styled-content style=\"fixed-case\">LDV<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">SOF<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">TDF<\/jats:styled-content>. Clinicians prescribing <jats:styled-content style=\"fixed-case\">LDV<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">SOF<\/jats:styled-content> to <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content>\u2013coinfected patients receiving <jats:styled-content style=\"fixed-case\">TDF<\/jats:styled-content> should be cautious about use with concomitant nephrotoxic medications and monitor markers of tubular dysfunction, including urinary phosphorus excretion, and renal injury at baseline and week 4 of therapy. Tenofovir alafenamide and alternative <jats:styled-content style=\"fixed-case\">DAA<\/jats:styled-content>s may also have a role in the management of patients at high risk for renal adverse effects from TDF.<\/jats:p>","DOI":"10.1002\/phar.1803","type":"journal-article","created":{"date-parts":[[2016,7,26]],"date-time":"2016-07-26T08:48:53Z","timestamp":1469522933000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Nephrotoxicity Associated with Concomitant Use of Ledipasvir\u2010Sofosbuvir and Tenofovir in a Patient with Hepatitis C Virus and Human Immunodeficiency Virus Coinfection"],"prefix":"10.1002","volume":"36","author":[{"given":"Kristen L.","family":"Bunnell","sequence":"first","affiliation":[{"name":"College of Pharmacy University of Illinois at Chicago Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Vibhakar","sequence":"additional","affiliation":[{"name":"Ruth M. Rothstein CORE Center Cook Country Health and Hospitals System Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert C.","family":"Glowacki","sequence":"additional","affiliation":[{"name":"College of Pharmacy University of Illinois at Chicago Chicago Illinois"},{"name":"John H. Stroger Jr. Hospital Cook County Health and Hospitals System Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen A.","family":"Gallagher","sequence":"additional","affiliation":[{"name":"Ruth M. Rothstein CORE Center Cook Country Health and Hospitals System Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert M.","family":"Osei","sequence":"additional","affiliation":[{"name":"John H. Stroger Jr. Hospital Cook County Health and Hospitals System Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Huhn","sequence":"additional","affiliation":[{"name":"Ruth M. Rothstein CORE Center Cook Country Health and Hospitals System Chicago Illinois"},{"name":"John H. Stroger Jr. Hospital Cook County Health and Hospitals System Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,9,21]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.185"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27950"},{"key":"e_1_2_5_4_1","unstructured":"Panel\u00a0on Antiretroviral Guidelines for Adults and Adolescents.Guidelines for the use of antiretroviral agents in HIV\u20101\u2010infected adults and adolescents: considerations for antiretroviral use in patients with coinfections. 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