|Changes in Bone Turnover Markers and Association with Decreased Total Bone Mineral Density (tBMD) in Treatment-naïve Subjects Taking Lopinavir/Ritonavir (LPV/r) Combined with Raltegravir (RAL) or Tenofovir/Emtricitabine (TDF/FTC)|| |
|T. Brown1, L. Fredrick2, D. Warren2, L.K. Toh2, B. Renjifo2, R. Trinh2, R. Qaqish2|
|1Johns Hopkins University, Baltimore, United States, 2AbbVie Inc., North Chicago, United States|
|Objectives: Prospective studies have reported a 2-6% BMD decrease through Wk96 after antiretroviral therapy(ART) initiation. It is unclear whether early changes in bone turnover markers predict bone loss following ART initiation. We evaluated changes in bone turnover markers in patients initiating LPV/r+RAL or LPV/r+TDF/FTC, and tested association of baseline marker levels and early changes from baseline with clinically significant bone loss at Wk96. |
Methods: ART-naïve, HIV-infected adults were randomized to receive LPV/r 400/100mgBID with RAL 400mgBID or TDF/FTC 300/200mgQD. Whole body dual-energy x-ray absorptiometry(DXA) scans assessed tBMD. Bone turnover markers including osteocalcin(OC), type I C-terminus telopeptide(CTx), procollagen type I propeptide(P1NP), and bone-specific alkaline phosphatase(BSAP) were measured from archived baseline, Wk4, Wk16, Wk48, and Wk96 specimens. Multivariable logistic regression tested association of treatment group, demographic/baseline characteristics, and baseline levels and early changes from baseline(Wk4 and Wk16)in turnover markers with tBMD decrease ≥5% at Wk96.
Results: 160/206 patients randomized(78 LPV/r+ RAL and 82 LPV/r+TDF/FTC)had DXA scans at baseline and Wk96. Overall, 19/160(11.9%)had a tBMD loss of ≥5% at Wk96(3/78[3.8%] LPV/r+RAL versus 16/82[19.5%] LPV/r+TDF/FTC, P=0.003). At Wk4, Wk16, Wk48, and Wk96, mean increase from baseline was significant for OC(P< 0.001) and CTx(P< 0.05) in both groups; mean increases were greater in the LPV/r+TDF/FTC group versus the LPV/r+RAL group at Wk16, Wk48, and Wk96 for OC(P< 0.05) and Wk4, Wk16, Wk48, and Wk96 for CTx(P≤0.001). P1NP mean decrease was significant only in the LPV/r+RAL group at Wk16 and Wk48(P< 0.05). BSAP mean changes were not significant at any timepoint. By multivariable analysis, factors independently associated with increased incidence of ≥5% tBMD reduction at Wk96 included TDF/FTC treatment, age ≥40 years, baseline CD4+ T-cells< 200 cells/mm3, and greater CTx increase from baseline to Wk4.
Conclusions: Early changes in CTx predicted ≥5% tBMD decrease at Wk96. Studies are needed to establish its utility to predict tBMD loss with ART initiation.
David Warren , AbbVie Inc. , North Chicago , United States
Assigned in sessions:
18.10.2013, 10:30-12:30, Parallel Session, PS7, Antiretroviral Therapy II, Bozar (Plenary Hall)