Edgar Turner Overton, MD; Ellen S. Chan, MSc; Todd T. Brown, MD, PhD; Pablo Tebas, MD; Grace A. McComsey, MD; Kathleen M. Melbourne, PharmD; Andrew Napoli, PhD; William Royce Hardin, BS; Heather J. Ribaudo, PhD; Michael T. Yin, MD, MS
Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health.
Acknowledgment: The authors thank the study sites and study patients for their time and effort. They also thank the members of the A5280 study team who contributed to the study: Jennifer Rothenberg, Kathy Watson, Lara Hosey, Bernadette Jarocki, Lynette Purdue, Allan Tenorio, and Amy Gonzalez.
Grant Support: By the National Institute of Allergy and Infectious Diseases (award number U01AI068636). Bristol-Myers Squibb and Gilead funded the DXA scans and ancillary laboratory testing. Study medications were provided by Bristol-Myers Squibb, Gilead Sciences, and Tishcon.
Disclosures: Dr. Overton reports grants from the National Institutes of Health during the conduct of the study and other from Gilead Sciences outside the submitted work. Ms. Chan reports grants from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, during the conduct of the study. Dr. Brown reports personal fees from Gilead Sciences, ViiV Healthcare, Merck, Abbvie, Theratechnologies, and EMD Serono outside the submitted work. Dr. Tebas reports consultancy with Merck and GlaxoSmithKline outside the submitted work. Dr. McComsey reports consultancy with Gilead Sciences, Bristol-Myers Squibb, Pfizer, and ViiV Healthcare; grants/grants pending from Gilead Sciences, Bristol-Myers Squibb, GlaxoSmithKline, and Merck; and payment for lectures from Bristol-Myers Squibb and Merck outside the submitted work. Ms. Melbourne reports other from Gilead Sciences outside the submitted work. Dr. Napoli reports other from Bristol-Myers Squibb outside the submitted work. Dr. Ribaudo reports grants from the Viiv Healthcare during the conduct of the study. Dr. Yin reports personal fees from Gilead and Abbvie and grants from the Viiv Healthcare outside the submitted work. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M14-1409.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer.
Reproducible Research Statement:Study protocol: Available from the AIDS Clinical Trials Group Leadership and Operations Center (e-mail, lrobertson3@partners.org). Statistical code and data set: Available from the AIDS Clinical Trials Group Statistical Data Analysis Center (e-mail, sdac.data@fstrf.org).
Requests for Single Reprints: Edgar Turner Overton, MD, University of Alabama School of Medicine, 908 20th Street South, CCB RM 330A, Birmingham, AL 35213; e-mail, toverton@uab.edu.
Current Author Addresses: Dr. Overton: Division of Infectious Diseases, University of Alabama School of Medicine, 908 20th Street South, CCB RM 330A, Birmingham, AL 35213.
Ms. Chan: Statistical & Data Analysis Center, Harvard School of Public Health, FXB Building, Room 539, 651 Huntington Avenue, Boston, MA 02115.
Dr. Brown: Division of Endocrinology and Metabolism, Johns Hopkins University, 1830 East Monument Street, Baltimore, MD 21287.
Dr. Tebas: Division of Infectious Diseases, University of Pennsylvania, 536 Johnson Pavilion, 36th Street and Hamilton Walk, Philadelphia, PA 19104.
Dr. McComsey: Division of Infectious Diseases, Case Western Reserve University, 1110 Euclid Avenue, Cleveland, OH 44106-4984.
Ms. Melbourne: Gilead Sciences, 50 Morris Street, Warwick, RI 02889.
Dr. Napoli: Bristol-Myers Squibb, 777 Scudders Mill Road, Plainsboro, NJ 08536-1615.
Mr. Hardin: Duke University Community Advisory Board, 1005 Iredell Street, Durham, NC 27705-4123.
Dr. Ribaudo: Statistical & Data Analysis Center, Harvard School of Public Health, FXB Building, Room 509, 651 Huntington Avenue, Boston, MA 02115.
Dr. Yin: Division of Infectious Diseases, Columbia University Medical Center, PH8-876, 630 West 168th Street, New York, NY 10032.
Author Contributions: Conception and design: E.T. Overton, E.S. Chan, T.T. Brown, P. Tebas, G.A. McComsey, K.M. Melbourne, H.J. Ribaudo, M.T. Yin.
Analysis and interpretation of the data: E.T. Overton, E.S. Chan, T.T. Brown, P. Tebas, G.A. McComsey, K.M. Melbourne, A. Napoli, H.J. Ribaudo, M.T. Yin.
Drafting of the article: E.T. Overton, E.S. Chan, T.T. Brown, W.R. Hardin, H.J. Ribaudo, M.T. Yin.
Critical revision of the article for important intellectual content: E.T. Overton, E.S. Chan, T.T. Brown, P. Tebas, G.A. McComsey, H.J. Ribaudo, M.T. Yin.
Final approval of the article: E.T. Overton, E.S. Chan, T.T. Brown, P. Tebas, G.A. McComsey, K.M. Melbourne, A. Napoli, W.R. Hardin, H.J. Ribaudo, M.T. Yin.
Provision of study materials or patients: A. Napoli.
Statistical expertise: E.S. Chan, H.J. Ribaudo.
Obtaining of funding: E.T. Overton, T.T. Brown, K.M. Melbourne, M.T. Yin.
Administrative, technical, or logistic support: K.M. Melbourne.
Collection and assembly of data: E.T. Overton, E.S. Chan, T.T. Brown, H.J. Ribaudo, M.T. Yin.
Antiretroviral therapy initiation for HIV-1 infection is associated with 2% to 6% loss of bone mineral density (BMD).
To evaluate the effect of vitamin D3 plus calcium supplementation on bone loss associated with antiretroviral therapy initiation.
48-week prospective, randomized, double-blind, placebo-controlled study. (ClinicalTrials.gov: NCT01403051)
39 AIDS Clinical Trials Group units.
Adults with antiretroviral therapy–naive HIV.
BMD by dual-energy x-ray absorptiometry, 25-hydroxyvitamin D levels, and other laboratory assessments.
165 eligible patients were randomly assigned (79 received vitamin D3 plus calcium and 86 received placebo). The study groups were well-balanced at baseline: 90% were men, 33% were non-Hispanic black, and the median CD4 count was 0.341 × 109 cells/L. At 48 weeks, the percentage of decline in total hip BMD was smaller in the vitamin D3 plus calcium group than in the placebo group: Medians were −1.36% (interquartile range [IQR], −3.43% to 0.50%) and −3.22% (IQR, −5.56% to −0.88%), respectively (P = 0.004). Similar results were seen at the lumbar spine. At 48 weeks, 90% of patients achieved HIV-1 RNA levels less than 50 copies/mL. Levels of 25-hydroxyvitamin D3 increased with vitamin D3 plus calcium but not with placebo: Median change was 61.2 nmol/L (IQR, 36.4 to 94.3) versus 1.7 nmol/L (IQR, −13.2 to 10.7) (P < 0.001). Overall, 103 patients (62%) reported 1 or more adverse event, with similar distribution between groups; no cases of hypercalcemia and 1 case of nephrolithiasis were reported in the placebo group.
No international sites were included, and follow-up was only 48 weeks.
Vitamin D3 plus calcium supplementation mitigates the BMD loss seen with initiation of efavirenz/emtricitabine/tenofovir disoproxil fumarate.
National Institute of Allergy and Infectious Diseases, Bristol-Myers Squibb, and Gilead Sciences.
Overton ET, Chan ES, Brown TT, Tebas P, McComsey GA, Melbourne KM, et al. Vitamin D and Calcium Attenuate Bone Loss With Antiretroviral Therapy Initiation: A Randomized Trial. Ann Intern Med. 2015;162:815–824. doi: 10.7326/M14-1409
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© 2019
Published: Ann Intern Med. 2015;162(12):815-824.
DOI: 10.7326/M14-1409
Endocrine and Metabolism, HIV, Infectious Disease, Metabolic Bone Disorders.