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Clinical Trial
. 2013 Sep-Oct;14(5):224-34.
doi: 10.1310/hct1405-224.

Bone mineral density effects of randomized regimen and nucleoside reverse transcriptase inhibitor selection from ACTG A5142

Jeannie S Huang  1 , Michael D Hughes, Sharon A Riddler, Richard H Haubrich; Aids Clinical Trials Group A5142 Study Team
Affiliations
Clinical Trial

Bone mineral density effects of randomized regimen and nucleoside reverse transcriptase inhibitor selection from ACTG A5142

Jeannie S Huang et al. HIV Clin Trials. 2013 Sep-Oct.

Abstract

Objective: To compare the longitudinal changes in total bone mineral density (TBMD) across antiretroviral (ARV) regimens.

Methods: A5142 was an open-label study comparing 3 ARV regimens for the initial treatment of HIV-1. Subjects were randomized equally to efavirenz (EFV) plus 2 nucleoside reverse transcriptase inhibitors (NRTIs), lopinavir/ritonavir (LPV/r) plus 2 NRTIs, or LPV/r plus EFV without NRTI. The NRTI regimen (lamivudine [3TC] plus zidovudine [ZDV], stavudine [d4T], or tenofovir [TDF]) was selected prior to randomization. TBMD was assessed via whole-body dual-energy X-ray absorptiometry (DXA) at baseline and 48 and 96 weeks. Analysis was modified intent-to-treat (ITT) ignoring regimen changes using all evaluations.

Results: Significant mean declines in TBMD at week 48 were observed among subjects. In repeated-measures analysis of changes (including randomized regimen, NRTI used, and time), there was a significant difference in the NRTI-containing arms in mean percentage change in TBMD at week 48 according to NRTI used (P < .001). Subjects taking ZDV had similar changes to those taking d4T (P = .970), whereas those taking TDF had larger declines (P < .001). There was a nonsignificant trend toward greater mean declines among subjects taking LPV/r versus EFV (P = .080). Overall, TDF-containing regimens demonstrated the greatest losses in TBMD, while EFV regimens without TDF had lesser TBMD reductions even compared to the NRTI-sparing arm. From week 48 to 96, all treatment groups continued to lose TBMD at similar rates.

Conclusions: Among NRTI-containing arms, NRTI selection, especially use of TDF, had a greater effect on TBMD change than randomized regimen. The long-term clinical significance remains to be demonstrated.

Keywords: HIV; antiretroviral therapy; bone density.

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Conflict of interest statement

Conflicts of interest: R.H. reports having received honoraria or consultant fees from Abbot, Bristol-Myers Squibb, Gilead Sciences, Vertex, and Tibotec and research support (to UCSD) from Abbott, GlaxoSmithKline, Merck, Pfizer, and ViiV. M.D.H. is a paid data monitoring committee member for Boehringer Ingelheim, Medicines Development, Pfizer, and Tibotec. S.R. and J.S.H. report no conflicts.

Figures

Figure 1
Figure 1
Mean total bone mineral density (TBMD) percentage change from baseline over time according to antiretroviral (ARV) regimen. (A) Modified intent-to-treat (ITT) population. (B) As-treated (AS) population. (C) Model-based estimated TBMD changes (modified ITT population). d4T = stavudine; EFV = efavirenz; LPV = lopinavir/ ritonavir; TDF = tenofovir; Sparing = efavirenz plus lopinavir/ ritonavir; ZDV = zidovudine. Note: Changes for ZDV and d4T plots were intentionally offset for display purposes. There was no difference between ZDV and d4T found in the model.
Figure 1
Figure 1
Mean total bone mineral density (TBMD) percentage change from baseline over time according to antiretroviral (ARV) regimen. (A) Modified intent-to-treat (ITT) population. (B) As-treated (AS) population. (C) Model-based estimated TBMD changes (modified ITT population). d4T = stavudine; EFV = efavirenz; LPV = lopinavir/ ritonavir; TDF = tenofovir; Sparing = efavirenz plus lopinavir/ ritonavir; ZDV = zidovudine. Note: Changes for ZDV and d4T plots were intentionally offset for display purposes. There was no difference between ZDV and d4T found in the model.
Figure 1
Figure 1
Mean total bone mineral density (TBMD) percentage change from baseline over time according to antiretroviral (ARV) regimen. (A) Modified intent-to-treat (ITT) population. (B) As-treated (AS) population. (C) Model-based estimated TBMD changes (modified ITT population). d4T = stavudine; EFV = efavirenz; LPV = lopinavir/ ritonavir; TDF = tenofovir; Sparing = efavirenz plus lopinavir/ ritonavir; ZDV = zidovudine. Note: Changes for ZDV and d4T plots were intentionally offset for display purposes. There was no difference between ZDV and d4T found in the model.
See this image and copyright information in PMC

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