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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

doi: 10.1097/QAD.0b013e32832c4947
Clinical Science

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.

aVU University Medical Center, Department of Internal Medicine, The Netherlands

bInternational Antiviral Therapy Evaluation Center, The Netherlands

cOnze Lieve Vrouwe Gasthuis, Department of Internal Medicine, The Netherlands

dAcademic Medical Center, Department of Infectious Diseases, Tropical Medicine and AIDS and Center for Infection and Immunity, Amsterdam, The Netherlands

eHelsinki University Central Hospital, Department of Internal Medicine, Helsinki, Finland.

* Current affiliation: Medisch Centrum Leeuwarden, Leeuwarden, The Netherlands.

Received 17 January, 2009

Revised 27 March, 2009

Accepted 30 March, 2009

Correspondence to M.G.A. van Vonderen, MD, VU University Medical Center, Department of Internal Medicine 4A35, PO Box 7057, 1007 MB Amsterdam, The Netherlands. E-mail:

© 2009 Lippincott Williams & Wilkins, Inc.