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We previously showed long-acting antiresorptive zoledronic acid (ZOL) prevented ART-induced bone loss through 48 weeks of therapy and here investigate whether protection persisted.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We randomized 63 nonosteoporotic, treatment-naive adult PWH initiating ART to ZOL (5 mg) versus placebo in a double-blinded, placebo-controlled, phase IIb trial. Here we analyzed the long-term outcome data (144 weeks). Plasma bone turnover markers and bone mineral density (BMD) were quantified at weeks 0, 12, 24, 48, 96, and 144. Primary outcome was change in bone resorption marker C-terminal telopeptide of collagen (CTx). Repeated-measures analyses using mixed linear models were used to estimate and compare study endpoints.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>At 96 weeks, mean CTx was 62% lower with ZOL relative to placebo (n = 46; CTx = 0.123 vs 0.324 ng\/mL; P &amp;lt; .001); at 144 weeks a 25% difference between arms was not statistically significant. At 48 weeks, lumbar spine BMD with ZOL was 11% higher than placebo (n = 60; P &amp;lt; .001) and remained 9\u201311% higher at 96 (n = 46) and 144 (n = 41; P &amp;lt; .001) weeks. 144 weeks after ZOL infusion, BMD did not change at the lumbar spine (P = .22) but declined at the hip (P = .04) and femoral neck (P = .02).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>A single dose of ZOL administered at ART initiation blunts bone resorption and BMD loss at key fracture-prone anatomical sites in treatment-naive PWH for 3 years. A multicenter randomized phase III clinical trial validating these results in a larger population is needed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical Trials Registration<\/jats:title><jats:p>NCT01228318.<\/jats:p><\/jats:sec>","DOI":"10.1093\/cid\/ciz1027","type":"journal-article","created":{"date-parts":[[2019,10,14]],"date-time":"2019-10-14T11:42:43Z","timestamp":1571053363000},"page":"1655-1663","source":"Crossref","is-referenced-by-count":16,"title":["Antiretroviral Therapy\u2013Induced Bone Loss Is Durably Suppressed by a Single Dose of Zoledronic Acid in Treatment-Naive Persons with Human Immunodeficiency Virus Infection: A Phase IIB Trial"],"prefix":"10.1093","volume":"71","author":[{"given":"Ighovwerha","family":"Ofotokun","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA"},{"name":"Grady Health System, Atlanta, Georgia, 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