Effects of Emtricitabine/Tenofovir on Bone Mineral Density in HIV-Negative Persons in a Randomized, Double-Blind, Placebo-Controlled Trial

Kathleen Mulligan; David V. Glidden; Peter L. Anderson; Albert Liu; Vanessa McMahan; Pedro Gonzales; Maria Esther Ramirez-Cardich; Sirianong Namwongprom; Piotr Chodacki; Laura Maria Carvalo De Mendonca; Furong Wang; Javier R. Lama; Suwat Chariyalertsak; Juan Vicente Guanira; Susan Buchbinder; Linda Gail Bekker; Mauro Schechter; Valdilea G. Veloso; Robert M. Grant; Lorena Vargas; Jorge Sanchez; Chiang Mai; Pongpun Saokhieo; Kerry Murphy; Hailey Gilmore; Sally Holland; Elizabeth Faber; John Duda; Linda Bewerunge; Elizabeth Batist; Christine Hoskin; Ben Brown; Rio De Janeiro; Carina Beppu-Yoshida; Marcellus Dias Da Costa; Sergio Carlos Assis De Jesus; Jose Roberto Grangeiro Da Silva; Roberta Millan; Brenda Regina De Siqueira Hoagland; Nilo Martinez Fernandes; Lucilene Da Silva Freitas; Beatriz Grinsztejn; Jose Pilotto; Lane Bushman; Jia Hua Zheng; Louis Anthony Guida; Brandon Kline; Pedro Goicochea; Jonathan Manzo; Robert Hance; Jeff McConnell; Patricia Defechereux; Vivian Levy; Malu Robles; Brian Postle; David Burns; James Rooney

doi:10.1093/cid/civ324

Effects of Emtricitabine/Tenofovir on Bone Mineral Density in HIV-Negative Persons in a Randomized, Double-Blind, Placebo-Controlled Trial

Kathleen Mulligan, David V. Glidden, Peter L. Anderson, Albert Liu, Vanessa McMahan, Pedro Gonzales, Maria Esther Ramirez-Cardich, Sirianong Namwongprom, Piotr Chodacki, Laura Maria Carvalo De Mendonca, Furong Wang, Javier R. Lama, Suwat Chariyalertsak, Juan Vicente Guanira, Susan Buchbinder, Linda Gail Bekker, Mauro Schechter, Valdilea G. Veloso, Robert M. Grant, Lorena VargasJorge Sanchez, Chiang Mai, Pongpun Saokhieo, Kerry Murphy, Hailey Gilmore, Sally Holland, Elizabeth Faber, John Duda, Linda Bewerunge, Elizabeth Batist, Christine Hoskin, Ben Brown, Rio De Janeiro, Carina Beppu-Yoshida, Marcellus Dias Da Costa, Sergio Carlos Assis De Jesus, Jose Roberto Grangeiro Da Silva, Roberta Millan, Brenda Regina De Siqueira Hoagland, Nilo Martinez Fernandes, Lucilene Da Silva Freitas, Beatriz Grinsztejn, Jose Pilotto, Lane Bushman, Jia Hua Zheng, Louis Anthony Guida, Brandon Kline, Pedro Goicochea, Jonathan Manzo, Robert Hance, Jeff McConnell, Patricia Defechereux, Vivian Levy, Malu Robles, Brian Postle, David Burns, James Rooney

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

122 Scopus citations

Abstract

Background. Daily preexposure prophylaxis (PrEP) with oral emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) decreases the risk of human immunodeficiency virus (HIV) acquisition. Initiation of TDF decreases bone mineral density (BMD) in HIV-infected people. We report the effect of FTC/TDF on BMD in HIV-seronegative men who have sex with men and in transgender women. Methods. Dual-energy X-ray absorptiometry was performed at baseline and 24-week intervals in a substudy of iPrEx, a randomized, double-blind, placebo-controlled trial of FTC/TDF PrEP. Plasma and intracellular tenofovir concentrations were measured in participants randomized to FTC/TDF. Results. In 498 participants (247 FTC/TDF, 251 placebo), BMD in those randomized to FTC/TDF decreased modestly but statistically significantly by 24 weeks in the spine (net difference, -0.91% [95% confidence interval {CI}, -1.44% to -.38%]; P =. 001) and hip (-0.61% [95% CI, -.96% to -.27%], P =. 001). Changes within each subsequent 24-week interval were not statistically significant. Changes in BMD by week 24 correlated inversely with intracellular tenofovir diphosphate (TFV-DP), which was detected in 53% of those randomized to FTC/TDF. Net BMD loss by week 24 in participants with TFV-DP levels indicative of consistent dosing averaged -1.42% ± 29% and -0.85% ± 19% in the spine and hip, respectively (P <. 001 vs placebo). Spine BMD tended to rebound following discontinuation of FTC/TDF. There were no differences in fractures (P =. 62) or incidence of low BMD. Conclusions. In HIV-uninfected persons, FTC/TDF PrEP was associated with small but statistically significant decreases in BMD by week 24 that inversely correlated with TFV-DP, with more stable BMD thereafter.

Original language	English (US)
Pages (from-to)	572-580
Number of pages	9
Journal	Clinical Infectious Diseases
Volume	61
Issue number	4
DOIs	https://doi.org/10.1093/cid/civ324
State	Published - Aug 15 2015
Externally published	Yes

Keywords

DXA
PrEP
bone
emtricitabine
tenofovir

ASJC Scopus subject areas

Microbiology (medical)
Infectious Diseases

UN SDGs

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

Access to Document

10.1093/cid/civ324

Cite this

Mulligan, K., Glidden, D. V., Anderson, P. L., Liu, A., McMahan, V., Gonzales, P., Ramirez-Cardich, M. E., Namwongprom, S., Chodacki, P., De Mendonca, L. M. C., Wang, F., Lama, J. R., Chariyalertsak, S., Guanira, J. V., Buchbinder, S., Bekker, L. G., Schechter, M., Veloso, V. G., Grant, R. M., ... Rooney, J. (2015). Effects of Emtricitabine/Tenofovir on Bone Mineral Density in HIV-Negative Persons in a Randomized, Double-Blind, Placebo-Controlled Trial. Clinical Infectious Diseases, 61(4), 572-580. https://doi.org/10.1093/cid/civ324

Mulligan, K, Glidden, DV, Anderson, PL, Liu, A, McMahan, V, Gonzales, P, Ramirez-Cardich, ME, Namwongprom, S, Chodacki, P, De Mendonca, LMC, Wang, F, Lama, JR, Chariyalertsak, S, Guanira, JV, Buchbinder, S, Bekker, LG, Schechter, M, Veloso, VG, Grant, RM, Vargas, L, Sanchez, J, Mai, C, Saokhieo, P, Murphy, K, Gilmore, H, Holland, S, Faber, E, Duda, J, Bewerunge, L, Batist, E, Hoskin, C, Brown, B, De Janeiro, R, Beppu-Yoshida, C, Da Costa, MD, Assis De Jesus, SC, Grangeiro Da Silva, JR, Millan, R, De Siqueira Hoagland, BR, Martinez Fernandes, N, Da Silva Freitas, L, Grinsztejn, B, Pilotto, J, Bushman, L, Zheng, JH, Anthony Guida, L, Kline, B, Goicochea, P, Manzo, J, Hance, R, McConnell, J, Defechereux, P, Levy, V, Robles, M, Postle, B, Burns, D & Rooney, J 2015, 'Effects of Emtricitabine/Tenofovir on Bone Mineral Density in HIV-Negative Persons in a Randomized, Double-Blind, Placebo-Controlled Trial', Clinical Infectious Diseases, vol. 61, no. 4, pp. 572-580. https://doi.org/10.1093/cid/civ324

@article{244ef88a8b914c9490f1e196d3535d48,

title = "Effects of Emtricitabine/Tenofovir on Bone Mineral Density in HIV-Negative Persons in a Randomized, Double-Blind, Placebo-Controlled Trial",

abstract = "Background. Daily preexposure prophylaxis (PrEP) with oral emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) decreases the risk of human immunodeficiency virus (HIV) acquisition. Initiation of TDF decreases bone mineral density (BMD) in HIV-infected people. We report the effect of FTC/TDF on BMD in HIV-seronegative men who have sex with men and in transgender women. Methods. Dual-energy X-ray absorptiometry was performed at baseline and 24-week intervals in a substudy of iPrEx, a randomized, double-blind, placebo-controlled trial of FTC/TDF PrEP. Plasma and intracellular tenofovir concentrations were measured in participants randomized to FTC/TDF. Results. In 498 participants (247 FTC/TDF, 251 placebo), BMD in those randomized to FTC/TDF decreased modestly but statistically significantly by 24 weeks in the spine (net difference, -0.91% [95% confidence interval {CI}, -1.44% to -.38%]; P =. 001) and hip (-0.61% [95% CI, -.96% to -.27%], P =. 001). Changes within each subsequent 24-week interval were not statistically significant. Changes in BMD by week 24 correlated inversely with intracellular tenofovir diphosphate (TFV-DP), which was detected in 53% of those randomized to FTC/TDF. Net BMD loss by week 24 in participants with TFV-DP levels indicative of consistent dosing averaged -1.42% ± 29% and -0.85% ± 19% in the spine and hip, respectively (P <. 001 vs placebo). Spine BMD tended to rebound following discontinuation of FTC/TDF. There were no differences in fractures (P =. 62) or incidence of low BMD. Conclusions. In HIV-uninfected persons, FTC/TDF PrEP was associated with small but statistically significant decreases in BMD by week 24 that inversely correlated with TFV-DP, with more stable BMD thereafter.",

keywords = "DXA, PrEP, bone, emtricitabine, tenofovir",

author = "Kathleen Mulligan and Glidden, {David V.} and Anderson, {Peter L.} and Albert Liu and Vanessa McMahan and Pedro Gonzales and Ramirez-Cardich, {Maria Esther} and Sirianong Namwongprom and Piotr Chodacki and {De Mendonca}, {Laura Maria Carvalo} and Furong Wang and Lama, {Javier R.} and Suwat Chariyalertsak and Guanira, {Juan Vicente} and Susan Buchbinder and Bekker, {Linda Gail} and Mauro Schechter and Veloso, {Valdilea G.} and Grant, {Robert M.} and Lorena Vargas and Jorge Sanchez and Chiang Mai and Pongpun Saokhieo and Kerry Murphy and Hailey Gilmore and Sally Holland and Elizabeth Faber and John Duda and Linda Bewerunge and Elizabeth Batist and Christine Hoskin and Ben Brown and {De Janeiro}, Rio and Carina Beppu-Yoshida and {Da Costa}, {Marcellus Dias} and {Assis De Jesus}, {Sergio Carlos} and {Grangeiro Da Silva}, {Jose Roberto} and Roberta Millan and {De Siqueira Hoagland}, {Brenda Regina} and {Martinez Fernandes}, Nilo and {Da Silva Freitas}, Lucilene and Beatriz Grinsztejn and Jose Pilotto and Lane Bushman and Zheng, {Jia Hua} and {Anthony Guida}, Louis and Brandon Kline and Pedro Goicochea and Jonathan Manzo and Robert Hance and Jeff McConnell and Patricia Defechereux and Vivian Levy and Malu Robles and Brian Postle and David Burns and James Rooney",

note = "Publisher Copyright: {\textcopyright} 2015 The Author 2015.",

year = "2015",

month = aug,

day = "15",

doi = "10.1093/cid/civ324",

language = "English (US)",

volume = "61",

pages = "572--580",

journal = "Clinical Infectious Diseases",

issn = "1058-4838",

publisher = "Oxford University Press",

number = "4",

}

TY - JOUR

T1 - Effects of Emtricitabine/Tenofovir on Bone Mineral Density in HIV-Negative Persons in a Randomized, Double-Blind, Placebo-Controlled Trial

AU - Mulligan, Kathleen

AU - Glidden, David V.

AU - Anderson, Peter L.

AU - Liu, Albert

AU - McMahan, Vanessa

AU - Gonzales, Pedro

AU - Ramirez-Cardich, Maria Esther

AU - Namwongprom, Sirianong

AU - Chodacki, Piotr

AU - De Mendonca, Laura Maria Carvalo

AU - Wang, Furong

AU - Lama, Javier R.

AU - Chariyalertsak, Suwat

AU - Guanira, Juan Vicente

AU - Buchbinder, Susan

AU - Bekker, Linda Gail

AU - Schechter, Mauro

AU - Veloso, Valdilea G.

AU - Grant, Robert M.

AU - Vargas, Lorena

AU - Sanchez, Jorge

AU - Mai, Chiang

AU - Saokhieo, Pongpun

AU - Murphy, Kerry

AU - Gilmore, Hailey

AU - Holland, Sally

AU - Faber, Elizabeth

AU - Duda, John

AU - Bewerunge, Linda

AU - Batist, Elizabeth

AU - Hoskin, Christine

AU - Brown, Ben

AU - De Janeiro, Rio

AU - Beppu-Yoshida, Carina

AU - Da Costa, Marcellus Dias

AU - Assis De Jesus, Sergio Carlos

AU - Grangeiro Da Silva, Jose Roberto

AU - Millan, Roberta

AU - De Siqueira Hoagland, Brenda Regina

AU - Martinez Fernandes, Nilo

AU - Da Silva Freitas, Lucilene

AU - Grinsztejn, Beatriz

AU - Pilotto, Jose

AU - Bushman, Lane

AU - Zheng, Jia Hua

AU - Anthony Guida, Louis

AU - Kline, Brandon

AU - Goicochea, Pedro

AU - Manzo, Jonathan

AU - Hance, Robert

AU - McConnell, Jeff

AU - Defechereux, Patricia

AU - Levy, Vivian

AU - Robles, Malu

AU - Postle, Brian

AU - Burns, David

AU - Rooney, James

PY - 2015/8/15

Y1 - 2015/8/15

N2 - Background. Daily preexposure prophylaxis (PrEP) with oral emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) decreases the risk of human immunodeficiency virus (HIV) acquisition. Initiation of TDF decreases bone mineral density (BMD) in HIV-infected people. We report the effect of FTC/TDF on BMD in HIV-seronegative men who have sex with men and in transgender women. Methods. Dual-energy X-ray absorptiometry was performed at baseline and 24-week intervals in a substudy of iPrEx, a randomized, double-blind, placebo-controlled trial of FTC/TDF PrEP. Plasma and intracellular tenofovir concentrations were measured in participants randomized to FTC/TDF. Results. In 498 participants (247 FTC/TDF, 251 placebo), BMD in those randomized to FTC/TDF decreased modestly but statistically significantly by 24 weeks in the spine (net difference, -0.91% [95% confidence interval {CI}, -1.44% to -.38%]; P =. 001) and hip (-0.61% [95% CI, -.96% to -.27%], P =. 001). Changes within each subsequent 24-week interval were not statistically significant. Changes in BMD by week 24 correlated inversely with intracellular tenofovir diphosphate (TFV-DP), which was detected in 53% of those randomized to FTC/TDF. Net BMD loss by week 24 in participants with TFV-DP levels indicative of consistent dosing averaged -1.42% ± 29% and -0.85% ± 19% in the spine and hip, respectively (P <. 001 vs placebo). Spine BMD tended to rebound following discontinuation of FTC/TDF. There were no differences in fractures (P =. 62) or incidence of low BMD. Conclusions. In HIV-uninfected persons, FTC/TDF PrEP was associated with small but statistically significant decreases in BMD by week 24 that inversely correlated with TFV-DP, with more stable BMD thereafter.

AB - Background. Daily preexposure prophylaxis (PrEP) with oral emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) decreases the risk of human immunodeficiency virus (HIV) acquisition. Initiation of TDF decreases bone mineral density (BMD) in HIV-infected people. We report the effect of FTC/TDF on BMD in HIV-seronegative men who have sex with men and in transgender women. Methods. Dual-energy X-ray absorptiometry was performed at baseline and 24-week intervals in a substudy of iPrEx, a randomized, double-blind, placebo-controlled trial of FTC/TDF PrEP. Plasma and intracellular tenofovir concentrations were measured in participants randomized to FTC/TDF. Results. In 498 participants (247 FTC/TDF, 251 placebo), BMD in those randomized to FTC/TDF decreased modestly but statistically significantly by 24 weeks in the spine (net difference, -0.91% [95% confidence interval {CI}, -1.44% to -.38%]; P =. 001) and hip (-0.61% [95% CI, -.96% to -.27%], P =. 001). Changes within each subsequent 24-week interval were not statistically significant. Changes in BMD by week 24 correlated inversely with intracellular tenofovir diphosphate (TFV-DP), which was detected in 53% of those randomized to FTC/TDF. Net BMD loss by week 24 in participants with TFV-DP levels indicative of consistent dosing averaged -1.42% ± 29% and -0.85% ± 19% in the spine and hip, respectively (P <. 001 vs placebo). Spine BMD tended to rebound following discontinuation of FTC/TDF. There were no differences in fractures (P =. 62) or incidence of low BMD. Conclusions. In HIV-uninfected persons, FTC/TDF PrEP was associated with small but statistically significant decreases in BMD by week 24 that inversely correlated with TFV-DP, with more stable BMD thereafter.

KW - DXA

KW - PrEP

KW - bone

KW - emtricitabine

KW - tenofovir

UR - http://www.scopus.com/inward/record.url?scp=84938598621&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84938598621&partnerID=8YFLogxK

U2 - 10.1093/cid/civ324

DO - 10.1093/cid/civ324

M3 - Article

C2 - 25908682

AN - SCOPUS:84938598621

SN - 1058-4838

VL - 61

SP - 572

EP - 580

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

IS - 4

ER -

Effects of Emtricitabine/Tenofovir on Bone Mineral Density in HIV-Negative Persons in a Randomized, Double-Blind, Placebo-Controlled Trial

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this