Vitamin D3 Supplementation Increases Spine Bone Mineral Density in Adolescents and Young Adults with Human Immunodeficiency Virus Infection Being Treated with Tenofovir Disoproxil Fumarate: A Randomized, Placebo-Controlled Trial

Peter L. Havens; Charles B. Stephensen; Marta D. Van Loan; Gertrud U. Schuster; Leslie R. Woodhouse; Patricia M. Flynn; Catherine M. Gordon; Cynthia G. Pan; Brandy Rutledge; D. Robert Harris; Georgine Price; Alyne Baker; William A. Meyer; Craig M. Wilson; Rohan Hazra; Bill G. Kapogiannis; Kathleen Mulligan; Kavya Vellala; Justin Wheeler; Roger Fielding; Tammy Freytag; Joseph Domek; Erik Gertz; Patricia Emmanuel; Diane Straub; Elizabeth Enriquez-Bruce; Marvin Belzer; Diane Tucker; Larry D'Angelo; Connie Trexler; Steve Douglas; Mary Tanney; John H. Stroger; Miguel Martinez; Lisa Henry-Reid; Kelly Bojan; Donna Futterman; Maria Campos; Sue Ellen Abdalian; Leslie Kozina; Larry Friedman; Donna Maturo; Aditya Guar; Mary Dillard; Mary Paul; Jane Head; Liz Secord; Angulique Outlaw; Charnell Cromer; Allison Agwu; Renata Sanders; Thuy Anderson; Ken Mayer; Julian Dormitzer; Dan Reirden; Carrie Chambers; Andrea Kovacs; Eva Operskalski; James Homans; Allison Bearden; Susie Sanchez; Ana Puga; Zulma Eysallenne; Midnela Acevedo; Nicolas Rosario; Lourdes Angeli Nieves; Andrew Wiznia; Jacobo Abadi; Michael Rosenberg; Joanna Dobroszycki; Marlene Burey

doi:10.1093/cid/cix753

Vitamin D3 Supplementation Increases Spine Bone Mineral Density in Adolescents and Young Adults with Human Immunodeficiency Virus Infection Being Treated with Tenofovir Disoproxil Fumarate: A Randomized, Placebo-Controlled Trial

Peter L. Havens, Charles B. Stephensen, Marta D. Van Loan, Gertrud U. Schuster, Leslie R. Woodhouse, Patricia M. Flynn, Catherine M. Gordon, Cynthia G. Pan, Brandy Rutledge, D. Robert Harris, Georgine Price, Alyne Baker, William A. Meyer, Craig M. Wilson, Rohan Hazra, Bill G. Kapogiannis, Kathleen Mulligan, Kavya Vellala, Justin Wheeler, Roger FieldingTammy Freytag, Joseph Domek, Erik Gertz, Patricia Emmanuel, Diane Straub, Elizabeth Enriquez-Bruce, Marvin Belzer, Diane Tucker, Larry D'Angelo, Connie Trexler, Steve Douglas, Mary Tanney, John H. Stroger, Miguel Martinez, Lisa Henry-Reid, Kelly Bojan, Donna Futterman, Maria Campos, Sue Ellen Abdalian, Leslie Kozina, Larry Friedman, Donna Maturo, Aditya Guar, Mary Dillard, Mary Paul, Jane Head, Liz Secord, Angulique Outlaw, Charnell Cromer, Allison Agwu, Renata Sanders, Thuy Anderson, Ken Mayer, Julian Dormitzer, Dan Reirden, Carrie Chambers, Andrea Kovacs, Eva Operskalski, James Homans, Allison Bearden, Susie Sanchez, Ana Puga, Zulma Eysallenne, Midnela Acevedo, Nicolas Rosario, Lourdes Angeli Nieves, Andrew Wiznia, Jacobo Abadi, Michael Rosenberg, Joanna Dobroszycki, Marlene Burey

Pediatrics

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Abstract

Background Tenofovir disoproxil fumarate (TDF) decreases bone mineral density (BMD). We hypothesized that Vitamin D3 (VITD3) would increase BMD in youth receiving TDF. Methods This was a randomized, double-blind, placebo-controlled trial of directly observed VITD3 vs placebo every 4 weeks for 48 weeks in youth aged 16-24 years with HIV, RNA load <200 copies/mL, taking TDF-containing combination antiretroviral therapy (TDF-cART) for ≥180 days. Participants (N = 214) received a daily multivitamin containing VITD3 400 IU and calcium 162 mg, plus monthly randomized VITD3 50000 IU (n = 109) or placebo (n = 105). Outcome was change from baseline to week 48 in lumbar spine BMD (LSBMD). Data presented are median (Q1, Q3). Results Participants were aged 22.0 (21.0, 23.0) years, 84% were male, and 74% were black/African American. At baseline, 62% had 25-hydroxy Vitamin D (25-OHD) <20 ng/mL. Multivitamin adherence was 49% (29%, 69%), and VITD3/placebo adherence 100% (100%, 100%). Vitamin D intake was 2020 (1914, 2168) and 284 (179, 394) IU/day, and serum 25-OHD concentration was 36.9 (30.5, 42.4) and 20.6 (14.4, 25.8) ng/mL at 48 weeks in VITD3 and placebo groups, respectively (P <.001). From baseline to week 48, LSBMD increased by 1.15% (-0.75% to 2.74%) in the VITD3 group (n = 99; P <.001) and 0.09% (-1.49% to 2.61%) in the placebo group (n = 89; P =.25), without between-group difference (P =.12). VITD3 group changes occurred with baseline 25-OHD <20 ng/mL (1.17% [-.82% to 2.90%]; P =.004) and ≥20 ng/mL (0.93% [-.26% to 2.15%]; P =.033). Conclusions For youth taking TDF-cART, LSBMD increased through 48 weeks with VITD3 plus multivitamin, but not with placebo plus multivitamin, independent of baseline Vitamin D status. Clinical Trials Registration NCT01751646.

Original language	English (US)
Pages (from-to)	220-228
Number of pages	9
Journal	Clinical Infectious Diseases
Volume	66
Issue number	2
DOIs	https://doi.org/10.1093/cid/cix753
State	Published - Jan 15 2018

Keywords

HIV infection
Vitamin D supplementation
bone mineral density
parathyroid hormone
tenofovir disoproxil fumarate

ASJC Scopus subject areas

Microbiology (medical)
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Havens, P. L., Stephensen, C. B., Van Loan, M. D., Schuster, G. U., Woodhouse, L. R., Flynn, P. M., Gordon, C. M., Pan, C. G., Rutledge, B., Harris, D. R., Price, G., Baker, A., Meyer, W. A., Wilson, C. M., Hazra, R., Kapogiannis, B. G., Mulligan, K., Vellala, K., Wheeler, J., ... Burey, M. (2018). Vitamin D3 Supplementation Increases Spine Bone Mineral Density in Adolescents and Young Adults with Human Immunodeficiency Virus Infection Being Treated with Tenofovir Disoproxil Fumarate: A Randomized, Placebo-Controlled Trial. Clinical Infectious Diseases, 66(2), 220-228. https://doi.org/10.1093/cid/cix753

Vitamin D3 Supplementation Increases Spine Bone Mineral Density in Adolescents and Young Adults with Human Immunodeficiency Virus Infection Being Treated with Tenofovir Disoproxil Fumarate : A Randomized, Placebo-Controlled Trial. / Havens, Peter L.; Stephensen, Charles B.; Van Loan, Marta D. et al.

In: Clinical Infectious Diseases, Vol. 66, No. 2, 15.01.2018, p. 220-228.

Research output: Contribution to journal › Article › peer-review

Havens, PL, Stephensen, CB, Van Loan, MD, Schuster, GU, Woodhouse, LR, Flynn, PM, Gordon, CM, Pan, CG, Rutledge, B, Harris, DR, Price, G, Baker, A, Meyer, WA, Wilson, CM, Hazra, R, Kapogiannis, BG, Mulligan, K, Vellala, K, Wheeler, J, Fielding, R, Freytag, T, Domek, J, Gertz, E, Emmanuel, P, Straub, D, Enriquez-Bruce, E, Belzer, M, Tucker, D, D'Angelo, L, Trexler, C, Douglas, S, Tanney, M, Stroger, JH, Martinez, M, Henry-Reid, L, Bojan, K, Futterman, D, Campos, M, Ellen Abdalian, S, Kozina, L, Friedman, L, Maturo, D, Guar, A, Dillard, M, Paul, M, Head, J, Secord, L, Outlaw, A, Cromer, C, Agwu, A, Sanders, R, Anderson, T, Mayer, K, Dormitzer, J, Reirden, D, Chambers, C, Kovacs, A, Operskalski, E, Homans, J, Bearden, A, Sanchez, S, Puga, A, Eysallenne, Z, Acevedo, M, Rosario, N, Nieves, LA, Wiznia, A, Abadi, J, Rosenberg, M, Dobroszycki, J & Burey, M 2018, 'Vitamin D3 Supplementation Increases Spine Bone Mineral Density in Adolescents and Young Adults with Human Immunodeficiency Virus Infection Being Treated with Tenofovir Disoproxil Fumarate: A Randomized, Placebo-Controlled Trial', Clinical Infectious Diseases, vol. 66, no. 2, pp. 220-228. https://doi.org/10.1093/cid/cix753

Havens PL, Stephensen CB, Van Loan MD, Schuster GU, Woodhouse LR, Flynn PM et al. Vitamin D3 Supplementation Increases Spine Bone Mineral Density in Adolescents and Young Adults with Human Immunodeficiency Virus Infection Being Treated with Tenofovir Disoproxil Fumarate: A Randomized, Placebo-Controlled Trial. Clinical Infectious Diseases. 2018 Jan 15;66(2):220-228. doi: 10.1093/cid/cix753

Havens, Peter L. ; Stephensen, Charles B. ; Van Loan, Marta D. et al. / Vitamin D3 Supplementation Increases Spine Bone Mineral Density in Adolescents and Young Adults with Human Immunodeficiency Virus Infection Being Treated with Tenofovir Disoproxil Fumarate : A Randomized, Placebo-Controlled Trial. In: Clinical Infectious Diseases. 2018 ; Vol. 66, No. 2. pp. 220-228.

@article{cd69cccb8657435fa65e8b062dc99608,

title = "Vitamin D3 Supplementation Increases Spine Bone Mineral Density in Adolescents and Young Adults with Human Immunodeficiency Virus Infection Being Treated with Tenofovir Disoproxil Fumarate: A Randomized, Placebo-Controlled Trial",

abstract = "Background Tenofovir disoproxil fumarate (TDF) decreases bone mineral density (BMD). We hypothesized that Vitamin D3 (VITD3) would increase BMD in youth receiving TDF. Methods This was a randomized, double-blind, placebo-controlled trial of directly observed VITD3 vs placebo every 4 weeks for 48 weeks in youth aged 16-24 years with HIV, RNA load <200 copies/mL, taking TDF-containing combination antiretroviral therapy (TDF-cART) for ≥180 days. Participants (N = 214) received a daily multivitamin containing VITD3 400 IU and calcium 162 mg, plus monthly randomized VITD3 50000 IU (n = 109) or placebo (n = 105). Outcome was change from baseline to week 48 in lumbar spine BMD (LSBMD). Data presented are median (Q1, Q3). Results Participants were aged 22.0 (21.0, 23.0) years, 84% were male, and 74% were black/African American. At baseline, 62% had 25-hydroxy Vitamin D (25-OHD) <20 ng/mL. Multivitamin adherence was 49% (29%, 69%), and VITD3/placebo adherence 100% (100%, 100%). Vitamin D intake was 2020 (1914, 2168) and 284 (179, 394) IU/day, and serum 25-OHD concentration was 36.9 (30.5, 42.4) and 20.6 (14.4, 25.8) ng/mL at 48 weeks in VITD3 and placebo groups, respectively (P <.001). From baseline to week 48, LSBMD increased by 1.15% (-0.75% to 2.74%) in the VITD3 group (n = 99; P <.001) and 0.09% (-1.49% to 2.61%) in the placebo group (n = 89; P =.25), without between-group difference (P =.12). VITD3 group changes occurred with baseline 25-OHD <20 ng/mL (1.17% [-.82% to 2.90%]; P =.004) and ≥20 ng/mL (0.93% [-.26% to 2.15%]; P =.033). Conclusions For youth taking TDF-cART, LSBMD increased through 48 weeks with VITD3 plus multivitamin, but not with placebo plus multivitamin, independent of baseline Vitamin D status. Clinical Trials Registration NCT01751646.",

keywords = "HIV infection, Vitamin D supplementation, bone mineral density, parathyroid hormone, tenofovir disoproxil fumarate",

author = "Havens, {Peter L.} and Stephensen, {Charles B.} and {Van Loan}, {Marta D.} and Schuster, {Gertrud U.} and Woodhouse, {Leslie R.} and Flynn, {Patricia M.} and Gordon, {Catherine M.} and Pan, {Cynthia G.} and Brandy Rutledge and Harris, {D. Robert} and Georgine Price and Alyne Baker and Meyer, {William A.} and Wilson, {Craig M.} and Rohan Hazra and Kapogiannis, {Bill G.} and Kathleen Mulligan and Kavya Vellala and Justin Wheeler and Roger Fielding and Tammy Freytag and Joseph Domek and Erik Gertz and Patricia Emmanuel and Diane Straub and Elizabeth Enriquez-Bruce and Marvin Belzer and Diane Tucker and Larry D'Angelo and Connie Trexler and Steve Douglas and Mary Tanney and Stroger, {John H.} and Miguel Martinez and Lisa Henry-Reid and Kelly Bojan and Donna Futterman and Maria Campos and {Ellen Abdalian}, Sue and Leslie Kozina and Larry Friedman and Donna Maturo and Aditya Guar and Mary Dillard and Mary Paul and Jane Head and Liz Secord and Angulique Outlaw and Charnell Cromer and Allison Agwu and Renata Sanders and Thuy Anderson and Ken Mayer and Julian Dormitzer and Dan Reirden and Carrie Chambers and Andrea Kovacs and Eva Operskalski and James Homans and Allison Bearden and Susie Sanchez and Ana Puga and Zulma Eysallenne and Midnela Acevedo and Nicolas Rosario and Nieves, {Lourdes Angeli} and Andrew Wiznia and Jacobo Abadi and Michael Rosenberg and Joanna Dobroszycki and Marlene Burey",

note = "Funding Information: Financial support. This work was supported by the ATN from the National Institutes of Health (grant numbers U01 HD 040533 and U01 HD 040474) through the NICHD (B. K.), with supplemental funding from the National Institute on Drug Abuse (S. Kahana) and National Institute of Mental Health (P. Brouwers, S. Allison). The study was scientifically reviewed by the ATN{\textquoteright}s Therapeutic Leadership Group. Network, scientific, and logistical support was provided by the ATN Coordinating Center (C. Wilson, C. Partlow) at the University of Alabama at Birmingham. Network operations and analytic support was provided by the ATN Data and Operations Center at Westat (D. R. Harris, B. Driver). Publisher Copyright: {\textcopyright} The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.",

year = "2018",

month = jan,

day = "15",

doi = "10.1093/cid/cix753",

language = "English (US)",

volume = "66",

pages = "220--228",

journal = "Clinical Infectious Diseases",

issn = "1058-4838",

publisher = "Oxford University Press",

number = "2",

}

TY - JOUR

T1 - Vitamin D3 Supplementation Increases Spine Bone Mineral Density in Adolescents and Young Adults with Human Immunodeficiency Virus Infection Being Treated with Tenofovir Disoproxil Fumarate

T2 - A Randomized, Placebo-Controlled Trial

AU - Havens, Peter L.

AU - Stephensen, Charles B.

AU - Van Loan, Marta D.

AU - Schuster, Gertrud U.

AU - Woodhouse, Leslie R.

AU - Flynn, Patricia M.

AU - Gordon, Catherine M.

AU - Pan, Cynthia G.

AU - Rutledge, Brandy

AU - Harris, D. Robert

AU - Price, Georgine

AU - Baker, Alyne

AU - Meyer, William A.

AU - Wilson, Craig M.

AU - Hazra, Rohan

AU - Kapogiannis, Bill G.

AU - Mulligan, Kathleen

AU - Vellala, Kavya

AU - Wheeler, Justin

AU - Fielding, Roger

AU - Freytag, Tammy

AU - Domek, Joseph

AU - Gertz, Erik

AU - Emmanuel, Patricia

AU - Straub, Diane

AU - Enriquez-Bruce, Elizabeth

AU - Belzer, Marvin

AU - Tucker, Diane

AU - D'Angelo, Larry

AU - Trexler, Connie

AU - Douglas, Steve

AU - Tanney, Mary

AU - Stroger, John H.

AU - Martinez, Miguel

AU - Henry-Reid, Lisa

AU - Bojan, Kelly

AU - Futterman, Donna

AU - Campos, Maria

AU - Ellen Abdalian, Sue

AU - Kozina, Leslie

AU - Friedman, Larry

AU - Maturo, Donna

AU - Guar, Aditya

AU - Dillard, Mary

AU - Paul, Mary

AU - Head, Jane

AU - Secord, Liz

AU - Outlaw, Angulique

AU - Cromer, Charnell

AU - Agwu, Allison

AU - Sanders, Renata

AU - Anderson, Thuy

AU - Mayer, Ken

AU - Dormitzer, Julian

AU - Reirden, Dan

AU - Chambers, Carrie

AU - Kovacs, Andrea

AU - Operskalski, Eva

AU - Homans, James

AU - Bearden, Allison

AU - Sanchez, Susie

AU - Puga, Ana

AU - Eysallenne, Zulma

AU - Acevedo, Midnela

AU - Rosario, Nicolas

AU - Nieves, Lourdes Angeli

AU - Wiznia, Andrew

AU - Abadi, Jacobo

AU - Rosenberg, Michael

AU - Dobroszycki, Joanna

AU - Burey, Marlene

N1 - Funding Information: Financial support. This work was supported by the ATN from the National Institutes of Health (grant numbers U01 HD 040533 and U01 HD 040474) through the NICHD (B. K.), with supplemental funding from the National Institute on Drug Abuse (S. Kahana) and National Institute of Mental Health (P. Brouwers, S. Allison). The study was scientifically reviewed by the ATN’s Therapeutic Leadership Group. Network, scientific, and logistical support was provided by the ATN Coordinating Center (C. Wilson, C. Partlow) at the University of Alabama at Birmingham. Network operations and analytic support was provided by the ATN Data and Operations Center at Westat (D. R. Harris, B. Driver). Publisher Copyright: © The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

PY - 2018/1/15

Y1 - 2018/1/15

N2 - Background Tenofovir disoproxil fumarate (TDF) decreases bone mineral density (BMD). We hypothesized that Vitamin D3 (VITD3) would increase BMD in youth receiving TDF. Methods This was a randomized, double-blind, placebo-controlled trial of directly observed VITD3 vs placebo every 4 weeks for 48 weeks in youth aged 16-24 years with HIV, RNA load <200 copies/mL, taking TDF-containing combination antiretroviral therapy (TDF-cART) for ≥180 days. Participants (N = 214) received a daily multivitamin containing VITD3 400 IU and calcium 162 mg, plus monthly randomized VITD3 50000 IU (n = 109) or placebo (n = 105). Outcome was change from baseline to week 48 in lumbar spine BMD (LSBMD). Data presented are median (Q1, Q3). Results Participants were aged 22.0 (21.0, 23.0) years, 84% were male, and 74% were black/African American. At baseline, 62% had 25-hydroxy Vitamin D (25-OHD) <20 ng/mL. Multivitamin adherence was 49% (29%, 69%), and VITD3/placebo adherence 100% (100%, 100%). Vitamin D intake was 2020 (1914, 2168) and 284 (179, 394) IU/day, and serum 25-OHD concentration was 36.9 (30.5, 42.4) and 20.6 (14.4, 25.8) ng/mL at 48 weeks in VITD3 and placebo groups, respectively (P <.001). From baseline to week 48, LSBMD increased by 1.15% (-0.75% to 2.74%) in the VITD3 group (n = 99; P <.001) and 0.09% (-1.49% to 2.61%) in the placebo group (n = 89; P =.25), without between-group difference (P =.12). VITD3 group changes occurred with baseline 25-OHD <20 ng/mL (1.17% [-.82% to 2.90%]; P =.004) and ≥20 ng/mL (0.93% [-.26% to 2.15%]; P =.033). Conclusions For youth taking TDF-cART, LSBMD increased through 48 weeks with VITD3 plus multivitamin, but not with placebo plus multivitamin, independent of baseline Vitamin D status. Clinical Trials Registration NCT01751646.

AB - Background Tenofovir disoproxil fumarate (TDF) decreases bone mineral density (BMD). We hypothesized that Vitamin D3 (VITD3) would increase BMD in youth receiving TDF. Methods This was a randomized, double-blind, placebo-controlled trial of directly observed VITD3 vs placebo every 4 weeks for 48 weeks in youth aged 16-24 years with HIV, RNA load <200 copies/mL, taking TDF-containing combination antiretroviral therapy (TDF-cART) for ≥180 days. Participants (N = 214) received a daily multivitamin containing VITD3 400 IU and calcium 162 mg, plus monthly randomized VITD3 50000 IU (n = 109) or placebo (n = 105). Outcome was change from baseline to week 48 in lumbar spine BMD (LSBMD). Data presented are median (Q1, Q3). Results Participants were aged 22.0 (21.0, 23.0) years, 84% were male, and 74% were black/African American. At baseline, 62% had 25-hydroxy Vitamin D (25-OHD) <20 ng/mL. Multivitamin adherence was 49% (29%, 69%), and VITD3/placebo adherence 100% (100%, 100%). Vitamin D intake was 2020 (1914, 2168) and 284 (179, 394) IU/day, and serum 25-OHD concentration was 36.9 (30.5, 42.4) and 20.6 (14.4, 25.8) ng/mL at 48 weeks in VITD3 and placebo groups, respectively (P <.001). From baseline to week 48, LSBMD increased by 1.15% (-0.75% to 2.74%) in the VITD3 group (n = 99; P <.001) and 0.09% (-1.49% to 2.61%) in the placebo group (n = 89; P =.25), without between-group difference (P =.12). VITD3 group changes occurred with baseline 25-OHD <20 ng/mL (1.17% [-.82% to 2.90%]; P =.004) and ≥20 ng/mL (0.93% [-.26% to 2.15%]; P =.033). Conclusions For youth taking TDF-cART, LSBMD increased through 48 weeks with VITD3 plus multivitamin, but not with placebo plus multivitamin, independent of baseline Vitamin D status. Clinical Trials Registration NCT01751646.

KW - HIV infection

KW - Vitamin D supplementation

KW - bone mineral density

KW - parathyroid hormone

KW - tenofovir disoproxil fumarate

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DO - 10.1093/cid/cix753

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SN - 1058-4838

VL - 66

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JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

IS - 2

ER -

Vitamin D3 Supplementation Increases Spine Bone Mineral Density in Adolescents and Young Adults with Human Immunodeficiency Virus Infection Being Treated with Tenofovir Disoproxil Fumarate: A Randomized, Placebo-Controlled Trial

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