First line zidovudine/lamivudine/lopinavir/ritonavir leads to greater bone loss compared to nevirapine/lopinavir/ritonavir

Objective: We studied changes in bone mineral density (BMD) and bone turnover after initiation of combination antiretroviral therapy (CART) and the contribution of zidovudine/lamivudine (ZDV/3TC) in particular. Design: Randomized clinical trial comparing lopinavir/ritonavir(LPV/r)+ZDV/3TC with LPV/r+nevirapine (NVP) in 50 cART-naive men. Methods: Dual energy X-ray absorptiometry (DXA) and quantitative computed tomography scans (QCT) were performed at baseline and 3, 12, and 24 months after CART initiation. Serum 25-hydroxy-vitamin D3, parathyroid hormone (PTH), osteocalcin, and urine deoxypyridinoline (DPD)/creatinine ratio were measured. Results: BMD decreased rapidly in both femoral neck and lumbar spine after cART initiation. BMD loss during 24 months measured by DXA, but not by QCT, was greater in the ZDV/3TC/LPV/r group compared to the NVP/LPV/r group [femoral neck: -6.3% +/- 1.0% (P<0.0001) compared to -2.3% +/- 0.9% (P=0.01), between-group P=0.0006); lumbar spine: -5.1% +/- 0.8% (P<0.0001) compared to -2.6% +/- 0.7% (P=0.0006), between-group P=0.071. Osteocalcin 1.+1.60 +/- 0.32 (P<0.0001) and +1.81 +/- 0.29 (P< 0.0001) nmol/l] and the urine DPD/creatinine ratio [+1.35 +/- 0.44 (P=0.0029) and +1.19 +/- 3=0.38 nmol/mmol (P=0.0024)] increased in both groups over 24 months, with no significant difference between groups. PTH increased to a greater degree in the NVP/LPV/r group [+2.0 +/- 0.31 pmol/l (P<0.0001)] compared to [+0.81 +/- 0.33 pmol/l (P=0.021) in the ZDV/3TC/LPV/r group]. Conclusion: BMD in both femoral neck and lumbar spine decreased rapidly after initiation of CART, in parallel to an increase in bone turnover. The greater bone loss in the ZDV/3TC/LPV/r group compared to the NVP/LPV/r group suggests that ZDV/3TC contributes to this process. The PTH increase does not explain this greater bone loss. (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins