Hip structural parameters over 96 weeks in HIV-infected adults switching treatment to tenofovir-emtricitabine or abacavir-lamivudine

Hila Haskelberg, Nicholas Pocock, Janaki Amin, Peter Robert Ebeling, Sean Emery, Andrew Carr, STEAL study investigators, Anthony Allworth, Anthony Allworth, Jonathan Anderson, David Baker, Mark Bloch, Mark Boyd, John Chuah, David Cooper, Stephen Davies, Linda Dayan, William Donohue, Nicholas Doong, Dominic Dwyer, John Dyer, Robert Finlayson, Michelle Giles, David Gordon, Mark Kelly, Nicholas Medland, Richard Moore, David Nolan, David Orth, Jeffrey Post, John Quin, Tim Read, Norman Roth, Darren Russell, David Shaw, David Smith, Don Smith, Alan Street, BanKiem Tee, Ian Woolley, Hila Haskelberg, Nicholas Pocock, Janaki Amin, Peter Robert Ebeling, Sean Emery, Andrew Carr, STEAL study investigators, Anthony Allworth, Anthony Allworth, Jonathan Anderson, David Baker, Mark Bloch, Mark Boyd, John Chuah, David Cooper, Stephen Davies, Linda Dayan, William Donohue, Nicholas Doong, Dominic Dwyer, John Dyer, Robert Finlayson, Michelle Giles, David Gordon, Mark Kelly, Nicholas Medland, Richard Moore, David Nolan, David Orth, Jeffrey Post, John Quin, Tim Read, Norman Roth, Darren Russell, David Shaw, David Smith, Don Smith, Alan Street, BanKiem Tee, Ian Woolley

Abstract

Background: Therapy with tenofovir is associated with lower bone mineral density (BMD), higher markers of bone turnover and increased fracture risk in HIV-infected adults. Bone structural parameters generated by hip structural analysis may represent a separate measure of bone strength, but have not been assessed in HIV.

Methods: Dual-energy X-ray absorptiometry (DXA) scans from 254 HIV-infected adults randomised to simplify their existing dual nucleoside analogue reverse transcriptase inhibitor therapy to coformulated tenofovir-emtricitabine or abacavir-lamivudine were analysed using DXA-derived hip structural analysis software. Hip structural parameters included femoral strength index, section modulus, cross-sectional area, and cross-sectional moment of inertia. We used one-way ANOVA to test the relationship between nucleoside analogue type at baseline and structural parameters, multivariable analysis to assess baseline covariates associated with femoral strength index, and t-tests to compare mean change in structural parameters over 96 weeks between randomised groups.

Results: Participants taking tenofovir at baseline had lower section modulus (-107.3 mm2, p = 0.001), lower cross-sectional area (-15.01 mm3, p = 0.001), and lower cross-sectional moment of inertia (-2,036.8 mm4, p = 0.007) than those receiving other nucleoside analogues. After adjustment for baseline risk factors, the association remained significant for section modulus (p = 0.008) and cross-sectional area (p = 0.002). Baseline covariates significantly associated with higher femoral strength index were higher spine T-score (p = 0.001), lower body fat mass (p<0.001), lower bone alkaline phosphatase (p = 0.025), and higher osteoprotegerin (p = 0.024). Hip structural parameters did not change significantly over 96 weeks and none was significantly affected by treatment simplification to tenofovir-emtricitabine or abacavir-lamivudine.

Conclusion: In this population, tenofovir use was associated with reduced composite indices of bone strength as measured by hip structural analysis, but none of the structural parameters improved significantly over 96 weeks with tenofovir cessation.

Trial registration: ClinicalTrials.gov NCT00192634.

Conflict of interest statement

Competing Interests: The authors have read the journal's policy and have the following conflicts: Sean Emery is a PLOS ONE Editorial Board member. Hila Haskelberg and Janaki Amin declare no conflict of interest. Nicolas Pocock received consultancy fees from Merck, Sanofi Aventis and Servier; and has served on an advisory board for Merck. Peter Ebeling's institution has received research funding from Merck; consultancy fees from Gilead Sciences and GlaxoSmithKline/ViiV Healthcare; and has served on an advisory board for Merck. Sean Emery has received research grant support from Abbvie, Gilead Sciences, Merck Research Laboratories, Pfizer, and ViiV Healthcare. Andrew Carr has received research funding from ViiV Healthcare, and Merck; consultancy fees from Gilead Sciences, ViiV Healthcare, MSD and Roche; lecture and travel sponsorships from Gilead Sciences, MSD, and ViiV Healthcare; and has served on advisory boards for Gilead Sciences, MSD, and ViiV Healthcare. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Figures

Figure 1. Patient disposition.
Figure 1. Patient disposition.
Figure 2. Hip structural parameters at baseline…
Figure 2. Hip structural parameters at baseline by type of NRTI at study entry (A) CSMI (bone's ability to resist bending), (B) CSA (bone's ability to resist axial compressive force) and (C) section modulus (bending strength).
Abbreviations: CSA, cross-sectional area; CSMI, cross-sectional moment of inertia.

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