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


CONCLUSIONS
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.


BACKGROUND
ClinicalTrials.gov NCT00192634.
The Kirby Institute, University of New South Wales, Sydney, Australia.
Hila
H
Haskelberg
St. Vincent's Hospital, Sydney, Australia.
Nicholas
N
Pocock
The Kirby Institute, University of New South Wales, Sydney, Australia.
Janaki
J
Amin
North West Academic Centre, University of Melbourne, Melbourne, Australia.
Peter Robert
PR
Ebeling
The Kirby Institute, University of New South Wales, Sydney, Australia.
Sean
S
Emery
St. Vincent's Hospital, Sydney, Australia.
Andrew
A
Carr
Anthony
A
Allworth
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D015519:Bone Density / Q000187:drug effects*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D015224:Dideoxynucleosides / Q000494:pharmacology* / Q000627:therapeutic use; D004338:Drug Combinations; D057915:Drug Substitution; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000000981:diagnostic imaging / Q000188:drug therapy*; D006621:Hip Joint / Q000000981:diagnostic imaging* / Q000187:drug effects; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D063065:Organophosphonates / Q000494:pharmacology* / Q000627:therapeutic use; D011859:Radiography; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000068698:Tenofovir; D016896:Treatment Outcome; D000099227:Abacavir
D000225:Adenine; D019380:Anti-HIV Agents; D003841:Deoxycytidine; D015224:Dideoxynucleosides; D004338:Drug Combinations; D000068679:Emtricitabine; D019259:Lamivudine; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir; C492871:abacavir, lamivudine drug combination; D000099227:Abacavir