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

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

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.

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.

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.