Title: Bone mineral density BMD changes until week 144 in a randomized trial of proteaseinhibitorsparing ve
1Bone mineral density (BMD) changes until week 144
in a randomized trial of protease-inhibitor-spari
ng versus nucleoside-analogue-sparing HAART
- Ann-Brit Eg Hansen, Court Pedersen, Henrik
Nielsen, Niels Obel, Jan Gerstoft - Rigshospitalet Copenhagen University Hospital
Odense University Hospital Aalborg University
Hospital, Denmark - A BMD substudy of the SPAR study
2Background
- High prevalence of osteopenia and osteoporosis
among HIV-infected persons - Results of prospective studies
- Nolan AIDS 2001, Mondy CID 2003,
- Bolland Clin Endocrinol 2007 - no decline
- Gallant (Gilead 903) JAMA 2004,
- Duvivier AIDS 2009 - initial decline
- Grund (SMART) AIDS 2009 - ongoing decline
Brown et al AIDS 2006, 202165-2174
3- Only few long-term randomized studies with BMD
measurements at hip and lumbar spine (Gilead 903,
SMART)
4AIM
- Primary aim
- to compare changes in BMD during 144 weeks in
HIV-infected patients initiating either
NA-sparing or PI-sparing HAART - Secondary aim
- to identify factors associated with changes in
BMD and with low baseline BMD
5Methodology
- BMD substudy of the investigator-initiated SPAR
trial - 104 HAART naive patients randomized to
- lopinavir/ritonavir 533/133 mg BID and efavirenz
600 mg QD - or
- zidovudine/lamivudine 150/300 mg BID and
efavirenz 600 mg QD - Primary endpoint peripheral fat loss
6BMD substudy
- Patients at 3 of 5 centers had lumbar spine
- and femoral neck BMD evaluated by DEXA
- baseline, week 24, 48, 96 and 144
- All patients with baseline BMD measurements and
at least one follow-up BMD measurement were
included - ITT and on class analyses
7Baseline characteristics
8 Percentage change in spine BMD from baseline,
ITT
NA-sparing
PI-sparing
Week 24. NA-sparing -2.7
PI-sparing -3.2 P0.49
Week 144. NA-sparing -2.5
PI-sparing -1.9 P0.67
9 Percentage change in hip BMD from baseline, ITT
NA-sparing
PI-sparing
Week 144. NA-sparing -4.5
PI-sparing -5.0 P0.73
Week 48. NA-sparing -5.1
PI-sparing -6.1 P0.49
10 Percentage change in spine BMD from baseline,
on class
NA-sparing
PI-sparing
Week 24. NA-sparing -2.3
PI-sparing -3.2 P0.38
Week 144. NA-sparing -0.2
PI-sparing -2.4 P0.18
11 Percentage change in hip BMD from baseline, on
class
NA-sparing
PI-sparing
Week 144. NA-sparing -4.8
PI-sparing -4.9 P0.49
Week 48. NA-sparing -5.7
PI-sparing -5.9 P0.87
12Predictors of change in spine BMD at week 24
13Predictors of change in hip BMD at week 24
14Predictors of baseline spine and hip BMD
Multivariable
Univariate
Hip
Multivariable
Univariate
Coef
.
Coef
Coef. (g/cm2)
.
Coef. (g/cm2)
P
-
value
P
-
value
P
-
value
P
-
value
CD4 cell count
CD4 cell count
-
0.003
0.30
-
0.004
0.42
-
-
(square
-
root)
(square
-
root)
BMI per unit
BMI per unit
0.22
0.006
0.55
0.0
0.
0.003
Multivariable analyses adjusted for CD4 cell
count/BMI, age, gender and current smoking
15Limitations
- No power calculations. Many drug discontinuations
- Results may not be valid for other NAs or PIs.
Could not analyze the potential influence of
NNRTIs
16Conclusion
- After initiation of HAART, BMD declined during
the first 24 (spine) to 48 weeks (hip) but
stabilized thereafter - Our study provided no evidence for a drug class
effect on BMD evolution, as decline was
independent of randomization to NA-sparing or
PI-sparing arm
17Interpretations
- The initial decline in BMD may be a result of
- delayed reversal of ongoing BMD loss in
immuno-suppressed individuals - a bone remodeling transient caused by HAART or
by HAART induced immune alterations ?
temporarily imbalance between bone resorption and
bone formation
Heany RP J Bone Miner Res 1994 91515-23
Aloia JF Osteporos Int 2008 191001-9
18Interpretations
- The initial decline in BMD may be a result of
- delayed reversal of ongoing BMD loss in
immuno-suppressed individuals - a bone remodeling transient caused by HAART or
by HAART induced immune alterations ?
temporarily imbalance between bone resorption and
bone formation
Heany RP J Bone Miner Res 1994 91515-23
Aloia JF Osteporos Int 2008 191001-9
19Acknowledgements
- Spar study investigators
- Jan Gerstoft
- Lars Mathiesen
- Court Pedersen
- Niels Obel
- Henrik Nielsen
- Alex Laursen
- Study participants
- Abbott, Denmark
- for an unconditional grant
- Study nurses
- Bente Baadegaard
- Lene Pors Jensen
- Kirsten Bødker
- Phillippa Collins
- Dorthe Pedersen
- Nete Bülow
- Lene Hergens
- Helle Møller
- Anita Nymark
- Iben Rose Loftheim
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22Spine, ITT, only completers
23HIP, ITT, only completers
24Treatment discontinuations