@article{c8f5392ce4b74765b9eccf9452ae5706,
title = "Bone mineral density reductions after tenofovir disoproxil fumarate initiation and changes in phosphaturia: A secondary analysis of ACTG A5224s",
abstract = "Background: It is unknown if the greater reductions in bone mineral density (BMD) associated with initiation of tenofovir disoproxil fumarate compared with abacavir in previously untreated HIV-infected participants in the ACTG A5224s clinical trial were associated with potentially worsening tenofovir-related phosphaturia. Methods: We correlated changes in BMD at the hip and spine with changes in phosphaturia [transtubular reabsorption of phosphorus (TRP) and tubular maximum phosphate reabsorption per glomerular filtration rate (TmP/GFR)] from entry through week 96 in those initiating tenofovir (n=134) versus abacavir (n=135) with efavirenz or atazanavir/ritonavir in A5224s. We also correlated changes in BMD with tenofovir AUC measured between weeks 4 and 24. Results: Changes in TRP and TmP/GFR through week 96 between the tenofovir and abacavir arms were not significantly different (both P≥0.70) and did not differ with use of efavirenz versus atazanavir/ritonavir. There were no significant correlations between changes in either TRP or TmP/GFR and with either hip or spine BMD in the tenofovir arms. Tenofovir AUC was significantly correlated with changes in hip BMD, but not spine BMD, at week 24 (r=-0.22, P=0.028) and week 48 (r=-0.26, P=0.010), but not at week 96 (r=-0.14, P=0.18). Conclusions: Changes in phosphaturia were not different between the tenofovir and abacavir arms in A5224s. Changes in hip and spine BMD with tenofovir were not related to changes in phosphaturia. However, tenofovir exposure was weakly associated with changes in hip BMD through week 48.",
author = "Gupta, {Samir K.} and Eunice Yeh and Kitch, {Douglas W.} and Brown, {Todd T.} and Venuto, {Charles S.} and Morse, {Gene D.} and Belinda Ha and Kathleen Melbourne and McComsey, {Grace A.}",
note = "Funding Information: This manuscript was presented in part at IDWeek 2016, New Orleans, LA, USA (Abstract 2188). We thank the study participants for their time and generosity. We also thank the ACTG A5224s study team, the participating sites and the site investigators: Sadia Shaik, MD and Ruben Lopez, MD, Harbor-UCLA Medical Center (Site 603) (CTU grant nos AI0694241, UL1-RR033176). Susan L. Koletar, MD and Diane Gochnour, RN, The Ohio State University Medical Center (Site 2301) (CTU grant no. AI069474). Geyoul Kim, RN and Mark Rodriguez, RN, Washington University (Site 2101) (CTU grant no. U01AI069495; GCRC grant no. UL1 RR024992). Elizabeth Lindsey, RN and Tamara James, BS, Alabama Therapeutics CRS (Site 5801) (CTU grant no. U01 AI069452). Ann C. Collier, MD and Jeffrey Schouten, MD, JD, University of Washington (Site 1401) (CTU grant no. AI069434; UL1 RR025014). Jorge L. Santana Bagur, MD and Santiago Marrero, MD, Puerto Rico-AIDS Clinical Trials Unit (Site 5401) (CTU grant no. 5 cc).Jenifer Baer, RN, BSN and Carl Fichtenbaum, MD, University of Cincinnati (Site 2401) (CTU grant no. AI069513). Patricia Walton, BSN, RN and Barbara Philpotts, BSN, RN, Case Western Reserve (Site 2501) (CTU grant no. AI69501). Princy Kumar, MD and Joseph Timpone, MD, Georgetown University (Site 1008) (CTU grant no. ACTG grant no. 5U01AI069494). Donna Pittard, RN BSN and David Currin, RN, University of North Carolina (Site 3201) (CTU grant no. 5-U01 AI069423-03; UNC CFAR no. P30 AI050410(-11); UNC CTRC no. UL 1RR 025747). Julie Hoffman, RN and Edward Seefried, RN, San Diego Medical Center UC (Site 701) (CTU grant no. AI69432). Susan Swindells, MBBS and Frances Van Meter, APRN, University of Nebraska (Site 1505) (CTU grant no. AI 27661). Deborah McMahon, MD and Barbara Rutecki, MSN, MPH, CRNP, University of Pittsburgh (Site 1001) (CTU grant no. 1 U01 AI069494-01). Michael P. Dube, MD and Martha Greenwald, RN, MSN, Indiana University (Site 2601) (CTU grant no. 5U01AI025859; GCRC no. M01 RR00750). Ilene Wiggins, RN and Eric Zimmerman, RN, Johns Hopkins University (Site 201) (CTU grant no. AI27668; CTSA grant no. UL1 RR025005). Judith Aberg, MD and Margarita Vasquez, RN, New York University/ NYCHHCat Bellevue Hospital Center (Site 401) (CTU grant no. AI27665, New grant no. AI069532). Martin McCarter and M. Graham Ray, RN, MSN, Colorado AIDS Clinical Trials Unit, (Site 6101) (CTU grant no. AI69450; RR025780). Mamta Jain, MD, PI and Tianna Petersen, MS, University of Texas Southwestern Medical Center (Site 3751) (CTU grant no. 3U01AI046376- 05S4). Emily Stumm, BS and Pablo Tebas, MD, University of Pennsylvania, Philadelphia (Site 6201) (CTU grant no. P30-AI0450008-11; CFAR grant no. UO1-AI069467-04). Mary Albrecht, MD and Neah Kim, NP, Beth Israel Deaconess (Partners/ Harvard) CRS (Site 103) (CTU grant no. U01 AI069472-04). Paul Edward Sax, MD and Joanne Delaney, RN, Brigham andWomen-s Hospital (Site 107) (CTU grant no. UOI AI 069472). Christine Hurley, RN and Roberto Corales, DO, AIDS Care (Site 1108) (CTU grant no. U01AI069511-02 [as of 2/12/08]; GCRC: UL1 RR 024160). Keith Henry, MD and Bette Bordenave, RN, Hennepin County Medical Center (Site 1502) (CTU grant no. N01 AI72626). Wendy Armstrong, MD and Ericka R. Patrick, RN, MSN, CCRC, Emory University HIV/AIDS Clinical Trails Unit (Site 5802) (CTU grant no. UO1Al69418-01/CFAR grant no. P30Al050409). Jane Reid RNC MS and Mary Adams RN MPh, University of Rochester (Site 1101) (CTU grant no. U01AI069511-02 [as of 2/12/08]; GCRC: UL1 RR 024160). Gene D. Morse, PharmD, FCCP, BCPS, SUNY, Buffalo, Erie County Medical Ctr. (Site 1102) (CTU grant no. AI27658). Michael P. Dube, MD and Martha Greenwald, RN, MSN, Wishard Memorial Hospital Indiana University (Site 2603) (CTU grant no. 5U01AI025859; GCRC no. M01 RR00750). Kimberly Y. Smith, MD, MPH and Joan A. Swiatek, APN, Rush University Medical Center (Site 2702) (CTU grant no. U01 AI069471). Nancy Hanks, RN and Debra Ogata-Arakaki, RN, University of Hawaii at Manoa, Leahi Hospital (Site 5201) (CTU grant no. AI34853). Ardis Moe, MD and Maria Palmer, PA-C, UCLA Medical Center (Site 601) (CTU grant no. U01AI069424-01). Jeffery Meier, MD and Jack T. Stapleton, MD, University of Iowa Hospitals and Clinics (Site 1504) (CTU grant no. UL1RR024979). Gary Matthew Cox, MD and Martha Silberman, RN, Duke University Medical Center Adult CRS (Site 1601) (CTU grant no. 5U01 AI069 484-02). Gerianne Casey, RN and William O-Brien MD, University of Texas, Galveston (Site 6301) (CTU grant no. AI32782). Valery Hughes, FNP and Todd Stroberg, RN, Cornell CRS (Sites 7803, 7804) (CTU grant no. U01 AI069419; CTSC no. UL1 RR024996). Nyef El-Daher, MD, McCree McCuller Wellness Center at the Connection (Site 1107) (CTU grant no. U01AI069511-02 [as of 2/12/08]; GCRC: UL1 RR 024160). Rebecca J. Basham, BS and Husamettin Erdem, MD, Vanderbilt Therapeutics CRS (Site 3652) (CTU grant no. AI46339-01; MO1 RR 00095).This work was supported by award numbers U01AI068636, AI068634 and AI38855 from the National Institute of Allergy and Infectious Diseases, and UL1 RR025005 from the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health. Study medications were provided by Abbott Pharmaceuticals, Bristol- Myers Squibb, Gilead Sciences and GlaxoSmithKline. Publisher Copyright: {\textcopyright} The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.",
year = "2017",
month = jul,
day = "1",
doi = "10.1093/jac/dkx076",
language = "English (US)",
volume = "72",
pages = "2042--2048",
journal = "Journal of Antimicrobial Chemotherapy",
issn = "0305-7453",
publisher = "Oxford University Press",
number = "7",
}