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.


METHODS
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].


CONCLUSIONS
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.
van Vonderen
Marit G A
MG
VU University Medical Center, Department of Internal Medicine, Amsterdam, The Netherlands. M.van.Vonderen@znb.nl
Lips
Paul
P
van Agtmael
Michiel A
MA
Hassink
Elly A M
EA
Brinkman
Kees
K
Geerlings
Suzanne E
SE
Sutinen
Jussi
J
Ristola
Matti
M
Danner
Sven A
SA
Reiss
Peter
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects*; D023241:Antiretroviral Therapy, Highly Active; D015519:Bone Density / Q000187:drug effects*; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D015497:HIV-1; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000009:adverse effects; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D019829:Nevirapine / Q000008:administration & dosage / Q000009:adverse effects; D010024:Osteoporosis / Q000139:chemically induced*; D011744:Pyrimidinones / Q000008:administration & dosage / Q000009:adverse effects; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects; D055815:Young Adult; D015215:Zidovudine / Q000008:administration & dosage / Q000009:adverse effects
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D061466:Lopinavir; D019259:Lamivudine; D015215:Zidovudine; D019829:Nevirapine; D019438:Ritonavir