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AIDS:
doi: 10.1097/QAD.0b013e32832c4947
Clinical Science

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

van Vonderen, Marit GAa,*; Lips, Paula; van Agtmael, Michiel Aa; Hassink, Elly AMb; Brinkman, Keesc; Geerlings, Suzanne Ed; Sutinen, Jussie; Ristola, Mattie; Danner, Sven Aa; Reiss, Peterd

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Abstract

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 = 0.07]. Osteocalcin [+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 ± 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.

© 2009 Lippincott Williams & Wilkins, Inc.

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