Less Bone Loss with Maraviroc- Versus Tenofovir-Containing Antiretroviral Therapy in the AIDS Clinical Trials Group A5303 Study

Babafemi O. Taiwo; Ellen S. Chan; Carl J. Fichtenbaum; Heather Ribaudo; Athe Tsibris; Karin L. Klingman; Joseph J. Eron; Baiba Berzins; Kevin Robertson; Alan Landay; Igho Ofotokun; Todd Brown; I. Martinez; Robert Kalayjian; Cara Wilson; Edward Acosta; David Rusin; Amy Gonzales; Orlando Roman; Kathy Melbourne; James Rooney; Alex Reinhart; Bryan Baugh; Roula Qaqish; Heera R. Jayvant; Laura Napolitano; Charles Walworth; Christos Petropoulos; John Davis; Mark Hite; Edward Seefried; Constance Benson; Nina Lambert; Karen Coleman; Tamara James; Amy Dill; Jenifer Baer; Christine Griesmer; Cathi Basler; Hector Bolivar; Margaret A. Fischl; Roberto C. Arduino; Aristoteles E. Villamil; Beverly Sha; Tondria Green; Brenda Jackson; Fred Nicotera; Geyoul Kim; Mark Rodrieguez; Annie Luetkemeyer; Jay Dwyer; Pamela Poethke; Aadia Rana; Miriam Chicurel-Bayard; Megan Telfer; Cornelius Van Dam; Timothy Lane; Ighovwerha Ofotokun; Melody Palmore; Patricia Walton; Felicia Williams; Jorge L. Santana; Olga I. Mendez; Pablo Tebas; Aleshia Thomas; Teri Flynn; Amy Sbrolla; Raphael Landovitz; Vanessa Cajahuaringa; Shelia Dunaway; Sheryl Storey; Ilene Wiggins; Andrea Weiss; Daniel Reirden; Hannah Bernath; Michael Yin; Jolene Noel-Connor; Rose Kim; Yolanda Smith; Paul Sax; Cheryl Keenan; Princy Kumar; Joseph Timpone; Michael P. DubCrossed Dsign; Bartolo Santos; Mary Adams; Christine Hurley

doi:10.1093/cid/civ455

Less Bone Loss with Maraviroc- Versus Tenofovir-Containing Antiretroviral Therapy in the AIDS Clinical Trials Group A5303 Study

Babafemi O. Taiwo, Ellen S. Chan, Carl J. Fichtenbaum, Heather Ribaudo, Athe Tsibris, Karin L. Klingman, Joseph J. Eron, Baiba Berzins, Kevin Robertson, Alan Landay, Igho Ofotokun, Todd Brown, I. Martinez, Robert Kalayjian, Cara Wilson, Edward Acosta, David Rusin, Amy Gonzales, Orlando Roman, Kathy MelbourneJames Rooney, Alex Reinhart, Bryan Baugh, Roula Qaqish, Heera R. Jayvant, Laura Napolitano, Charles Walworth, Christos Petropoulos, John Davis, Mark Hite, Edward Seefried, Constance Benson, Nina Lambert, Karen Coleman, Tamara James, Amy Dill, Jenifer Baer, Christine Griesmer, Cathi Basler, Hector Bolivar, Margaret A. Fischl, Roberto C. Arduino, Aristoteles E. Villamil, Beverly Sha, Tondria Green, Brenda Jackson, Fred Nicotera, Geyoul Kim, Mark Rodrieguez, Annie Luetkemeyer, Jay Dwyer, Pamela Poethke, Aadia Rana, Miriam Chicurel-Bayard, Megan Telfer, Cornelius Van Dam, Timothy Lane, Ighovwerha Ofotokun, Melody Palmore, Patricia Walton, Felicia Williams, Jorge L. Santana, Olga I. Mendez, Pablo Tebas, Aleshia Thomas, Teri Flynn, Amy Sbrolla, Raphael Landovitz, Vanessa Cajahuaringa, Shelia Dunaway, Sheryl Storey, Ilene Wiggins, Andrea Weiss, Daniel Reirden, Hannah Bernath, Michael Yin, Jolene Noel-Connor, Rose Kim, Yolanda Smith, Paul Sax, Cheryl Keenan, Princy Kumar, Joseph Timpone, Michael P. DubCrossed Dsign, Bartolo Santos, Mary Adams, Christine Hurley

School of Medicine

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

34 Scopus citations

Abstract

Background.There is a need to prevent or minimize bone loss associated with antiretroviral treatment (ART) initiation. We compared maraviroc (MVC)- to tenofovir disoproxil fumarate (TDF)-containing ART. Methods.This was a double-blind, placebo-controlled trial. ART-naive subjects with human immunodeficiency virus type 1 RNA load (viral load [VL]) >1000 copies/mL and R5 tropism were randomized to MVC 150 mg or TDF 300 mg once daily (1:1), stratified by VL <100 000 or ≥100 000 copies/mL and age <30 or ≥30 years. All subjects received darunavir 800 mg, ritonavir 100 mg, and emtricitabine 200 mg daily. Dual-energy X-ray absorptiometry scanning was done at baseline and week 48. The primary endpoint was percentage change in total hip bone mineral density (BMD) from baseline to week 48 in the as-treated population. Results.We enrolled 262 subjects. A total of 259 subjects (130 MVC, 129 TDF) contributed to the analyses (91% male; median age, 33 years; 45% white, 30% black, 22% Hispanic). Baseline median VL was 4.5 log₁₀ copies/mL and CD4 count was 390 cells/μL. The decline in hip BMD (n = 115 for MVC, n = 109 for TDF) at week 48 was less with MVC (median [Q1, Q3] of -1.51% [-2.93%, -0.11%] vs -2.40% [-4.30%, -1.32%] for TDF (P <. 001). Lumbar spine BMD decline was also less with MVC (median -0.88% vs -2.35%; P <. 001). Similar proportions of subjects in both arms achieved VL ≤50 copies/mL in as-treated and ITT analyses. Conclusions.MVC was associated with less bone loss at the hip and lumbar spine compared with TDF. MVC may be an option to attenuate ART-associated bone loss. Clinical Trials Registration.NCT01400412.

Original language	English (US)
Pages (from-to)	1179-1188
Number of pages	10
Journal	Clinical Infectious Diseases
Volume	61
Issue number	7
DOIs	https://doi.org/10.1093/cid/civ455
State	Published - Oct 1 2015

Keywords

bone
darunavir
maraviroc
tenofovir

ASJC Scopus subject areas

Microbiology (medical)
Infectious Diseases

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10.1093/cid/civ455

Cite this

Taiwo, B. O., Chan, E. S., Fichtenbaum, C. J., Ribaudo, H., Tsibris, A., Klingman, K. L., Eron, J. J., Berzins, B., Robertson, K., Landay, A., Ofotokun, I., Brown, T., Martinez, I., Kalayjian, R., Wilson, C., Acosta, E., Rusin, D., Gonzales, A., Roman, O., ... Hurley, C. (2015). Less Bone Loss with Maraviroc- Versus Tenofovir-Containing Antiretroviral Therapy in the AIDS Clinical Trials Group A5303 Study. Clinical Infectious Diseases, 61(7), 1179-1188. https://doi.org/10.1093/cid/civ455

Taiwo, BO, Chan, ES, Fichtenbaum, CJ, Ribaudo, H, Tsibris, A, Klingman, KL, Eron, JJ, Berzins, B, Robertson, K, Landay, A, Ofotokun, I, Brown, T, Martinez, I, Kalayjian, R, Wilson, C, Acosta, E, Rusin, D, Gonzales, A, Roman, O, Melbourne, K, Rooney, J, Reinhart, A, Baugh, B, Qaqish, R, Jayvant, HR, Napolitano, L, Walworth, C, Petropoulos, C, Davis, J, Hite, M, Seefried, E, Benson, C, Lambert, N, Coleman, K, James, T, Dill, A, Baer, J, Griesmer, C, Basler, C, Bolivar, H, Fischl, MA, Arduino, RC, Villamil, AE, Sha, B, Green, T, Jackson, B, Nicotera, F, Kim, G, Rodrieguez, M, Luetkemeyer, A, Dwyer, J, Poethke, P, Rana, A, Chicurel-Bayard, M, Telfer, M, Van Dam, C, Lane, T, Ofotokun, I, Palmore, M, Walton, P, Williams, F, Santana, JL, Mendez, OI, Tebas, P, Thomas, A, Flynn, T, Sbrolla, A, Landovitz, R, Cajahuaringa, V, Dunaway, S, Storey, S, Wiggins, I, Weiss, A, Reirden, D, Bernath, H, Yin, M, Noel-Connor, J, Kim, R, Smith, Y, Sax, P, Keenan, C, Kumar, P, Timpone, J, DubCrossed Dsign, MP, Santos, B, Adams, M & Hurley, C 2015, 'Less Bone Loss with Maraviroc- Versus Tenofovir-Containing Antiretroviral Therapy in the AIDS Clinical Trials Group A5303 Study', Clinical Infectious Diseases, vol. 61, no. 7, pp. 1179-1188. https://doi.org/10.1093/cid/civ455

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title = "Less Bone Loss with Maraviroc- Versus Tenofovir-Containing Antiretroviral Therapy in the AIDS Clinical Trials Group A5303 Study",

abstract = "Background.There is a need to prevent or minimize bone loss associated with antiretroviral treatment (ART) initiation. We compared maraviroc (MVC)- to tenofovir disoproxil fumarate (TDF)-containing ART. Methods.This was a double-blind, placebo-controlled trial. ART-naive subjects with human immunodeficiency virus type 1 RNA load (viral load [VL]) >1000 copies/mL and R5 tropism were randomized to MVC 150 mg or TDF 300 mg once daily (1:1), stratified by VL <100 000 or ≥100 000 copies/mL and age <30 or ≥30 years. All subjects received darunavir 800 mg, ritonavir 100 mg, and emtricitabine 200 mg daily. Dual-energy X-ray absorptiometry scanning was done at baseline and week 48. The primary endpoint was percentage change in total hip bone mineral density (BMD) from baseline to week 48 in the as-treated population. Results.We enrolled 262 subjects. A total of 259 subjects (130 MVC, 129 TDF) contributed to the analyses (91% male; median age, 33 years; 45% white, 30% black, 22% Hispanic). Baseline median VL was 4.5 log10 copies/mL and CD4 count was 390 cells/μL. The decline in hip BMD (n = 115 for MVC, n = 109 for TDF) at week 48 was less with MVC (median [Q1, Q3] of -1.51% [-2.93%, -0.11%] vs -2.40% [-4.30%, -1.32%] for TDF (P <. 001). Lumbar spine BMD decline was also less with MVC (median -0.88% vs -2.35%; P <. 001). Similar proportions of subjects in both arms achieved VL ≤50 copies/mL in as-treated and ITT analyses. Conclusions.MVC was associated with less bone loss at the hip and lumbar spine compared with TDF. MVC may be an option to attenuate ART-associated bone loss. Clinical Trials Registration.NCT01400412.",

keywords = "bone, darunavir, maraviroc, tenofovir",

author = "Taiwo, {Babafemi O.} and Chan, {Ellen S.} and Fichtenbaum, {Carl J.} and Heather Ribaudo and Athe Tsibris and Klingman, {Karin L.} and Eron, {Joseph J.} and Baiba Berzins and Kevin Robertson and Alan Landay and Igho Ofotokun and Todd Brown and I. Martinez and Robert Kalayjian and Cara Wilson and Edward Acosta and David Rusin and Amy Gonzales and Orlando Roman and Kathy Melbourne and James Rooney and Alex Reinhart and Bryan Baugh and Roula Qaqish and Jayvant, {Heera R.} and Laura Napolitano and Charles Walworth and Christos Petropoulos and John Davis and Mark Hite and Edward Seefried and Constance Benson and Nina Lambert and Karen Coleman and Tamara James and Amy Dill and Jenifer Baer and Christine Griesmer and Cathi Basler and Hector Bolivar and Fischl, {Margaret A.} and Arduino, {Roberto C.} and Villamil, {Aristoteles E.} and Beverly Sha and Tondria Green and Brenda Jackson and Fred Nicotera and Geyoul Kim and Mark Rodrieguez and Annie Luetkemeyer and Jay Dwyer and Pamela Poethke and Aadia Rana and Miriam Chicurel-Bayard and Megan Telfer and {Van Dam}, Cornelius and Timothy Lane and Ighovwerha Ofotokun and Melody Palmore and Patricia Walton and Felicia Williams and Santana, {Jorge L.} and Mendez, {Olga I.} and Pablo Tebas and Aleshia Thomas and Teri Flynn and Amy Sbrolla and Raphael Landovitz and Vanessa Cajahuaringa and Shelia Dunaway and Sheryl Storey and Ilene Wiggins and Andrea Weiss and Daniel Reirden and Hannah Bernath and Michael Yin and Jolene Noel-Connor and Rose Kim and Yolanda Smith and Paul Sax and Cheryl Keenan and Princy Kumar and Joseph Timpone and {DubCrossed Dsign}, {Michael P.} and Bartolo Santos and Mary Adams and Christine Hurley",

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

year = "2015",

month = oct,

day = "1",

doi = "10.1093/cid/civ455",

language = "English (US)",

volume = "61",

pages = "1179--1188",

journal = "Clinical Infectious Diseases",

issn = "1058-4838",

publisher = "Oxford University Press",

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TY - JOUR

T1 - Less Bone Loss with Maraviroc- Versus Tenofovir-Containing Antiretroviral Therapy in the AIDS Clinical Trials Group A5303 Study

AU - Taiwo, Babafemi O.

AU - Chan, Ellen S.

AU - Fichtenbaum, Carl J.

AU - Ribaudo, Heather

AU - Tsibris, Athe

AU - Klingman, Karin L.

AU - Eron, Joseph J.

AU - Berzins, Baiba

AU - Robertson, Kevin

AU - Landay, Alan

AU - Ofotokun, Igho

AU - Brown, Todd

AU - Martinez, I.

AU - Kalayjian, Robert

AU - Wilson, Cara

AU - Acosta, Edward

AU - Rusin, David

AU - Gonzales, Amy

AU - Roman, Orlando

AU - Melbourne, Kathy

AU - Rooney, James

AU - Reinhart, Alex

AU - Baugh, Bryan

AU - Qaqish, Roula

AU - Jayvant, Heera R.

AU - Napolitano, Laura

AU - Walworth, Charles

AU - Petropoulos, Christos

AU - Davis, John

AU - Hite, Mark

AU - Seefried, Edward

AU - Benson, Constance

AU - Lambert, Nina

AU - Coleman, Karen

AU - James, Tamara

AU - Dill, Amy

AU - Baer, Jenifer

AU - Griesmer, Christine

AU - Basler, Cathi

AU - Bolivar, Hector

AU - Fischl, Margaret A.

AU - Arduino, Roberto C.

AU - Villamil, Aristoteles E.

AU - Sha, Beverly

AU - Green, Tondria

AU - Jackson, Brenda

AU - Nicotera, Fred

AU - Kim, Geyoul

AU - Rodrieguez, Mark

AU - Luetkemeyer, Annie

AU - Dwyer, Jay

AU - Poethke, Pamela

AU - Rana, Aadia

AU - Chicurel-Bayard, Miriam

AU - Telfer, Megan

AU - Van Dam, Cornelius

AU - Lane, Timothy

AU - Ofotokun, Ighovwerha

AU - Palmore, Melody

AU - Walton, Patricia

AU - Williams, Felicia

AU - Santana, Jorge L.

AU - Mendez, Olga I.

AU - Tebas, Pablo

AU - Thomas, Aleshia

AU - Flynn, Teri

AU - Sbrolla, Amy

AU - Landovitz, Raphael

AU - Cajahuaringa, Vanessa

AU - Dunaway, Shelia

AU - Storey, Sheryl

AU - Wiggins, Ilene

AU - Weiss, Andrea

AU - Reirden, Daniel

AU - Bernath, Hannah

AU - Yin, Michael

AU - Noel-Connor, Jolene

AU - Kim, Rose

AU - Smith, Yolanda

AU - Sax, Paul

AU - Keenan, Cheryl

AU - Kumar, Princy

AU - Timpone, Joseph

AU - DubCrossed Dsign, Michael P.

AU - Santos, Bartolo

AU - Adams, Mary

AU - Hurley, Christine

PY - 2015/10/1

Y1 - 2015/10/1

N2 - Background.There is a need to prevent or minimize bone loss associated with antiretroviral treatment (ART) initiation. We compared maraviroc (MVC)- to tenofovir disoproxil fumarate (TDF)-containing ART. Methods.This was a double-blind, placebo-controlled trial. ART-naive subjects with human immunodeficiency virus type 1 RNA load (viral load [VL]) >1000 copies/mL and R5 tropism were randomized to MVC 150 mg or TDF 300 mg once daily (1:1), stratified by VL <100 000 or ≥100 000 copies/mL and age <30 or ≥30 years. All subjects received darunavir 800 mg, ritonavir 100 mg, and emtricitabine 200 mg daily. Dual-energy X-ray absorptiometry scanning was done at baseline and week 48. The primary endpoint was percentage change in total hip bone mineral density (BMD) from baseline to week 48 in the as-treated population. Results.We enrolled 262 subjects. A total of 259 subjects (130 MVC, 129 TDF) contributed to the analyses (91% male; median age, 33 years; 45% white, 30% black, 22% Hispanic). Baseline median VL was 4.5 log10 copies/mL and CD4 count was 390 cells/μL. The decline in hip BMD (n = 115 for MVC, n = 109 for TDF) at week 48 was less with MVC (median [Q1, Q3] of -1.51% [-2.93%, -0.11%] vs -2.40% [-4.30%, -1.32%] for TDF (P <. 001). Lumbar spine BMD decline was also less with MVC (median -0.88% vs -2.35%; P <. 001). Similar proportions of subjects in both arms achieved VL ≤50 copies/mL in as-treated and ITT analyses. Conclusions.MVC was associated with less bone loss at the hip and lumbar spine compared with TDF. MVC may be an option to attenuate ART-associated bone loss. Clinical Trials Registration.NCT01400412.

AB - Background.There is a need to prevent or minimize bone loss associated with antiretroviral treatment (ART) initiation. We compared maraviroc (MVC)- to tenofovir disoproxil fumarate (TDF)-containing ART. Methods.This was a double-blind, placebo-controlled trial. ART-naive subjects with human immunodeficiency virus type 1 RNA load (viral load [VL]) >1000 copies/mL and R5 tropism were randomized to MVC 150 mg or TDF 300 mg once daily (1:1), stratified by VL <100 000 or ≥100 000 copies/mL and age <30 or ≥30 years. All subjects received darunavir 800 mg, ritonavir 100 mg, and emtricitabine 200 mg daily. Dual-energy X-ray absorptiometry scanning was done at baseline and week 48. The primary endpoint was percentage change in total hip bone mineral density (BMD) from baseline to week 48 in the as-treated population. Results.We enrolled 262 subjects. A total of 259 subjects (130 MVC, 129 TDF) contributed to the analyses (91% male; median age, 33 years; 45% white, 30% black, 22% Hispanic). Baseline median VL was 4.5 log10 copies/mL and CD4 count was 390 cells/μL. The decline in hip BMD (n = 115 for MVC, n = 109 for TDF) at week 48 was less with MVC (median [Q1, Q3] of -1.51% [-2.93%, -0.11%] vs -2.40% [-4.30%, -1.32%] for TDF (P <. 001). Lumbar spine BMD decline was also less with MVC (median -0.88% vs -2.35%; P <. 001). Similar proportions of subjects in both arms achieved VL ≤50 copies/mL in as-treated and ITT analyses. Conclusions.MVC was associated with less bone loss at the hip and lumbar spine compared with TDF. MVC may be an option to attenuate ART-associated bone loss. Clinical Trials Registration.NCT01400412.

KW - bone

KW - darunavir

KW - maraviroc

KW - tenofovir

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SN - 1058-4838

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ER -

Less Bone Loss with Maraviroc- Versus Tenofovir-Containing Antiretroviral Therapy in the AIDS Clinical Trials Group A5303 Study

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