Samir K Gupta1, Eunice Yeh2, Douglas W Kitch2, Todd T Brown3, Charles S Venuto4, Gene D Morse5, Belinda Ha6, Kathleen Melbourne7, Grace A McComsey8. 1. Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA. 2. Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA. 3. Department of Medicine, Johns Hopkins University, Baltimore, MD 21287, USA. 4. Center for Human Experimental Therapeutics and Department of Neurology, University of Rochester, Rochester, NY 14642, USA. 5. School of Pharmacy and Pharmaceutical Sciences, University of Buffalo, State University of New York, Buffalo, NY 14203, USA. 6. GlaxoSmithKline/ViiV Healthcare, Research Triangle Park, NC 27709, USA. 7. Gilead Sciences, Foster City, CA 94404, USA. 8. Department of Pediatrics, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA.
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.
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.
Authors: José L Casado; Carmen Santiuste; Monica Vazquez; Sara Bañón; Marta Rosillo; Ana Gomez; María J Perez-Elías; Carmen Caballero; José M Rey; Santiago Moreno Journal: AIDS Date: 2016-06-01 Impact factor: 4.177
Authors: Mar Masiá; Sergio Padilla; Catalina Robledano; Natividad López; José Manuel Ramos; Felix Gutiérrez Journal: AIDS Res Hum Retroviruses Date: 2011-07-19 Impact factor: 2.205
Authors: Grace A McComsey; Douglas Kitch; Paul E Sax; Pablo Tebas; Camlin Tierney; Nasreen C Jahed; Laurie Myers; Kathleen Melbourne; Belinda Ha; Eric S Daar Journal: Clin Infect Dis Date: 2011-07-15 Impact factor: 9.079
Authors: Alexandra Calmy; Christoph A Fux; Richard Norris; Nathalie Vallier; Cécile Delhumeau; Katherine Samaras; Karl Hesse; Bernard Hirschel; David A Cooper; Andrew Carr Journal: J Infect Dis Date: 2009-12-01 Impact factor: 5.226
Authors: Andrew S Levey; Lesley A Stevens; Christopher H Schmid; Yaping Lucy Zhang; Alejandro F Castro; Harold I Feldman; John W Kusek; Paul Eggers; Frederick Van Lente; Tom Greene; Josef Coresh Journal: Ann Intern Med Date: 2009-05-05 Impact factor: 25.391
Authors: Lisa Hamzah; Amanda Samarawickrama; Lucy Campbell; Matthew Pope; Keith Burling; Martin Fisher; Yvonne Gilleece; Karen Walker-Bone; Frank A Post Journal: AIDS Date: 2015-09-10 Impact factor: 4.177
Authors: Lisa Hamzah; Juan M Tiraboschi; Helen Iveson; Martina Toby; Christine Mant; John Cason; Keith Burling; Emily Wandolo; Isabelle Jendrulek; Chris Taylor; Fowzia Ibrahim; Ranjababu Kulasegaram; Alastair Teague; Frank A Post; Julie Fox Journal: Antivir Ther Date: 2015-10-13
Authors: Robert C Kalayjian; Jeffrey M Albert; Serge Cremers; Samir K Gupta; Grace A McComsey; Karin L Klingman; Carl J Fichtenbaum; Todd T Brown; Babafemi O Taiwo Journal: AIDS Date: 2018-11-13 Impact factor: 4.177