TY - JOUR
T1 - Changes in bone turnover and bone loss in HIV-infected patients changing treatment to tenofovir-emtricitabine or abacavir-lamivudine
AU - Haskelberg, Hila
AU - Hoy, Jennifer F.
AU - Amin, Janaki
AU - Ebeling, Peter R.
AU - Emery, Sean
AU - Carr, Andrew
AU - Allworth, Anthony
AU - Anderson, Jonathan
AU - Baker, David
AU - Bloch, Mark
AU - Boyd, Mark
AU - Chuah, John
AU - Cooper, David
AU - Davies, Stephen
AU - Dayan, Linda
AU - Donohue, William
AU - Doong, Nicholas
AU - Dwyer, Dominic
AU - Dyer, John
AU - Finlayson, Robert
AU - Giles, Michelle
AU - Gordon, David
AU - Kelly, Mark
AU - Medland, Nicholas
AU - Moore, Richard
AU - Nolan, David
AU - Orth, David
AU - Post, Jeffrey
AU - Quin, John
AU - Read, Tim
AU - Roth, Norman
AU - Russell, Darren
AU - Shaw, David
AU - Smith, David
AU - Smith, Don
AU - Street, Alan
AU - Tee, Ban Kiem
AU - Woolley, Ian
N1 - Funding Information:
Co-author Sean Emery is a PLoS ONE Editorial Board member, Hila Haskelberg declares no conflict of interest. Jennifer Hoy’s institution has received research funding from GlaxoSmithKline/ViiV Healthcare, Gilead Sciences and Merck; travel sponsorship from Gilead Sciences, Janssen-Cilag, and Merck; and has served on advisory boards for Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline/ViiV Healthcare, Janssen-Cilag, Merck and Roche. Janaki Amin declares no conflict of interest. Peter Ebeling’s institution has received research funding from Merck; consultancy fees from Gilead Sciences and GlaxoSmithKline/ViiV Healthcare; and he has served on an advisory board for Merck. Sean Emery has either served on advisory boards; received travel grants, consultancy payments or honoraria from Abbott, BMS, Merck, Gilead, GSK, Tibotec, Viiv Healthcare, and Pfizer. Andrew Carr has received research funding from GlaxoSmithKline/ViiV Healthcare, and Merck; consultancy fees from Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline/ViiV Healthcare, Merck and Roche; lecture and travel sponsorships from Abbott, Boehringer- Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline/ViiV Healthcare, and Merck; and has served on advisory boards for Abbott, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline/ViiV Healthcare, Merck and Roche. This does not alter our adherence to all the PLoS ONE policies on sharing data and materials. Partial funding for the biomarker analysis was provided by GSK/ViiV Healthcare. This does not alter our adherence to all the PLoS ONE policies on sharing data and materials. In the STEAL main study, subjects were randomised to receive either of the following study drugs in combination with the remainder of their existing ART (having ceased the NRTI component): KivexaTM: ABC 600 mg+3 TC 300 mg FDC once daily TruvadaTM: FTC 200 mg+TDF 300 mg FDC once daily There are no other relevant declarations relating to employment, consultancy, patents, products in development or marketed products.
PY - 2012/6/15
Y1 - 2012/6/15
N2 - Background: Those receiving tenofovir/emtricitabine (TDF-FTC) had greater bone loss compared with abacavir/lamivudine (ABC-3TC) in a randomized simplification trial (STEAL study). Previous studies associated increased bone turnover and bone loss with initiation of antiretroviral treatment, however it is unclear whether change in bone mineral density (BMD) was a result of specific drugs, from immune reconstitution or from suppression of HIV replication. This analysis determined predictors of BMD change in the hip and spine by dual-energy x-ray absorptiometry in virologically suppressed participants through week 96. Methodology/Principal Findings: Bone turnover markers (BTMs) tested were: formation [bone alkaline phosphatase, procollagen type 1 N-terminal propeptide (P1NP)]; resorption (C-terminal cross-linking telopeptide of type 1 collagen [CTx]); and bone cytokine-signalling (osteoprotegerin, RANK ligand). Independent predictors of BMD change were determined using forward, stepwise, linear regression. BTM changes and fracture risk (FRAX®) at week 96 were compared by t-test. Baseline characteristics (n = 301) were: 98% male, mean age 45 years, current protease-inhibitor (PI) 23%, tenofovir/abacavir-naïve 52%. Independent baseline predictors of greater hip and spine bone loss were TDF-FTC randomisation (p≤0.013), lower fat mass (p-trend≤0.009), lower P1NP (p = 0.015), and higher hip T score/spine BMD (p-trend≤0.006). Baseline PI use was associated with greater spine bone loss (p = 0.004). TDF-FTC increased P1NP and CTx through Wk96 (p<0.01). Early changes in BTM did not predict bone loss at week 96. No significant between-group difference was found in fracture risk. Conclusions/Significance: Tenofovir/emtricitabine treatment, lower bone formation and lower fat mass predicted subsequent bone loss. There was no association between TDF-FTC and fracture risk.
AB - Background: Those receiving tenofovir/emtricitabine (TDF-FTC) had greater bone loss compared with abacavir/lamivudine (ABC-3TC) in a randomized simplification trial (STEAL study). Previous studies associated increased bone turnover and bone loss with initiation of antiretroviral treatment, however it is unclear whether change in bone mineral density (BMD) was a result of specific drugs, from immune reconstitution or from suppression of HIV replication. This analysis determined predictors of BMD change in the hip and spine by dual-energy x-ray absorptiometry in virologically suppressed participants through week 96. Methodology/Principal Findings: Bone turnover markers (BTMs) tested were: formation [bone alkaline phosphatase, procollagen type 1 N-terminal propeptide (P1NP)]; resorption (C-terminal cross-linking telopeptide of type 1 collagen [CTx]); and bone cytokine-signalling (osteoprotegerin, RANK ligand). Independent predictors of BMD change were determined using forward, stepwise, linear regression. BTM changes and fracture risk (FRAX®) at week 96 were compared by t-test. Baseline characteristics (n = 301) were: 98% male, mean age 45 years, current protease-inhibitor (PI) 23%, tenofovir/abacavir-naïve 52%. Independent baseline predictors of greater hip and spine bone loss were TDF-FTC randomisation (p≤0.013), lower fat mass (p-trend≤0.009), lower P1NP (p = 0.015), and higher hip T score/spine BMD (p-trend≤0.006). Baseline PI use was associated with greater spine bone loss (p = 0.004). TDF-FTC increased P1NP and CTx through Wk96 (p<0.01). Early changes in BTM did not predict bone loss at week 96. No significant between-group difference was found in fracture risk. Conclusions/Significance: Tenofovir/emtricitabine treatment, lower bone formation and lower fat mass predicted subsequent bone loss. There was no association between TDF-FTC and fracture risk.
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U2 - 10.1371/journal.pone.0038377
DO - 10.1371/journal.pone.0038377
M3 - Article
C2 - 22719882
AN - SCOPUS:84862490997
VL - 7
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 6
M1 - e38377
ER -