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Limb and Trunk Fat Changes by Total Body DEXA After 96 Weeks of Treatment with Once-Daily (QD) Fosamprenavir Boosted with Either 100 mg or 200 mg of Ritonavir (/r) plus Abacavir (ABC)/lamivudine (3TC): COL100758
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"After 96 weeks treatment with once-daily FPV/r + ABC/3TC, both limb and trunk fat depots generally increased. Changes in regional fat were not significantly different between those assigned FPV/r100 vs. FPV/r200" author conclusion".... "A >20% loss of fat was observed in upper limbs in 18% vs. 13% and in lower limbs in 15% vs. 6%; a >20% gain in trunk fat occurred in 38% vs. 45% of patients." (from Jules: my question is it possible that the fat loss some patients experienced in the limbs is due in part to reasons other than HIV or ART?)
Reported by Jules Levin
ICAAC/IDSA Oct 28 2008 Wash DC
D.A. Wohl1, E Dejesus2, L Sloan3, M Sension4, Q Liao, K appa5, K Oie5, C Hicks6
1Univ of NC, Chapel Hill, NC, 2Orlando Immun Ctr, Orlando, FL, TXID Consultants, Dallas, TX, 4Comprehensive Care Ctr, Ft Lauderdale, FL, 5GSK RTP, C, 6Duke Univ, Durham, NC
AUTHOR DISCUSSION
After 96 weeks of therapy with FPV/r + ABC/3TC:
-- Leg and trunk fat increased in both the FPV/r100 and FPV/r200 study groups.
-- Arm fat increased early during study follow-up but had returned to baseline among those receiving FPV/r100. The difference between study groups in the change in arm fat at Week 96 was not statistically significant (p=0.52) and there was considerable variability in values within each group.
-- No patient with available paired Baseline and Week 96 DEXA data had simultaneous increases>20% in trunk fat and either combined arm or leg fat decreases >20%.
-- There were no statistically significant differences between study groups in the median changes in regional body fat.
-- L-spine BMD dropped by 2%-3% within the group of 27 subjects who had data available, with no significant difference observed when comparing the study arms. (from Jules: it appears they used whole-body dexas to evaluate changes in bone density, and there is a question that whole body dexas may not be reliable at measuring bone density at specific places; you appear to need to use bone dexas.)
AUTHOR CONCLUSIONS
As has been observed in other recent trials among treatment-naïve patients, limb and trunk fat increased during the study, while BMD tended to decline.
In addition to providing similar virologic and immunologic responses among 115 treatment-naïve study participants, dosing of FPV with 100 mg versus 200 mg of ritonavir daily was not associated with significantly different changes in regional fat depots, BMD or fasting lipid parameters (data not shown).
The effect of differential adherence to ritonavir between the two arms on changes in metabolic parameters is worth examination. However, overall levels of adherence to ritonavir in this trial were high (>88%).
ABSTRACT
Objectives: To evaluate changes in regional fat and bone mineral density (BMD) after 96 weeks of treatment with once-daily fosamprenavir boosted with two different doses of ritonavir (100mg vs. 200mg) in patients receiving ABC/3TC.
Methods: COL100758 was an open-label, randomized study evaluating FPV/r 1400mg/100mg (FPV/r100) or FPV/r 1400mg/200mg (FPV/r200) + ABC/3TC 600mg/300mg given once daily in 115 ART-naïve patients. Total body DEXA was obtained pre-treatment and at weeks 48, 72 and 96 using Hologic or Lunar scanners. Median percent changes in fat were reported for upper and lower limbs and trunk. Median percent change in total body BMD and L-spine BMD were reported (L-spine BMD data were only available from centers with Hologic scanners). P-values were obtained using Wilcoxon rank-sum test. Clinically relevant changes in fat mass were defined as >20% loss for limb fat and/or >20% gain in trunk fat.
Results:
71 patients had paired baseline and Week 96 DEXA scans (81% male, 58% non-white, median age 39 years).
All results are reported as changes from baseline to 96 weeks for FPV/r100 (N=40) vs. FPV/r200 (N=31), respectively.
The median percent change in fat mass in all regions studied was not significantly different between the study groups: -1.5% vs. +11.6% for upper limbs [p=.51], +10.0% vs. +16.3% for lower limbs [p=.39], and +14.5% vs. +18.5% for trunk [p=.88].
A >20% loss of fat was observed in upper limbs in 18% vs. 13% and in lower limbs in 15% vs. 6%; a >20% gain in trunk fat occurred in 38% vs. 45% of patients.
No patient had simultaneous limb fat loss >20% and trunk fat gain >20%.
Median total body BMD (g/cm2) percent changes were: -1.05% vs. -1.04 [p=.29], and -3.0% vs. -2.2% for the 27 patients with L-spine data [p=.68].
Conclusions: After 96 weeks treatment with once-daily FPV/r + ABC/3TC, both limb and trunk fat depots generally increased. Changes in regional fat were not significantly different between those assigned FPV/r100 vs. FPV/r200. BMD changes were small in both study arms.
INTRODUCTION
Previously, we reported similar virologic and immunologic responses were achieved when FPV is boosted with 100 mg or 200 mg of ritonavir once daily in 115 ART-naïve patients also receiving ABC/3TC. 1
After 48 weeks of treatment, no significant differences were observed in the change from baseline in fasting cholesterol subsets or triglycerides. Additionally, there was no significant differences between study arms in change in limb fat or trunk fat; however, at
48 weeks there was a trend toward greater loss of bone mineral density (BMD) among those randomized to 200 mg of ritonavir. 2
We now present 96 week data on the differential affects of coadministration of FPV with 200 mg vs. 100 mg of ritonavir on body fat composition and BMD using whole body dual-energy X-ray absorptiometry (DEXA) in antiretroviral treatment-naïve men and women.
METHODS
Study regimens
Participants were randomized to receive 1400 mg of FPV once daily along with 100 mg of ritonavir (FPV/r100) versus 200 mg of ritonavir (FPV/r200). All received fixed dose abacavir/lamivudine (ABC/3TC), and (7) patients presumed hypersensitive to ABC were allowed to remain on study upon switching to zidovudine (ZDV)/3TC.
Body Fat Composition
Whole body DEXA scans (using Hologic and Lunar Scanners) were obtained at study entry and weeks 48 and 96. 80% of patients were evaluated with Hologic scanners.
Changes in regional fat including combined upper limbs, combined lower limbs and trunk were compared between study groups. The proportion of patients in each group with >20% (combined) arm fat decrease, >20% (combined) leg fat decrease or >20% trunk fat increase were compared.
Bone Density
Bone mineral density (BMD) was evaluated at study entry and weeks 48 and 96 by whole body DEXA scanning. Changes in total body and L-spine BMD were compared between study groups.
Adherence
Pill counts were obtained at each visit and adherence calculated as total number of pills missing/total number of pills prescribed.
Statistical Methods
Percent changes in arm fat, leg fat, trunk fat, and total body and L-spine BMD between the 2 treatment arms were compared using Wilcoxon rank-sum test. Comparisons of proportion of patients with clinically relevant fat changes were made using Fisher exact test.
RESULTS
References
1. Hicks et al., "Once-Daily Fosamprenavir (FPV) Boosted with Either 100mg or 200mg of Ritonavir (r) Along with Abacavir (ABC)/Lamivudine (3TC): 48 Week Safety and Efficacy Results from COL100758", poster P5.7/01, 11th European AIDS Conference, 25-26 October 2007, Madrid, Spain
2. Wohl et al., "Determination of Body Composition Changes by Total Body Dual-Energy X-ray Absorptiometry after 48 Weeks of Treatment with Once-Daily Fosamprenavir (FPV) Boosted with Two Different Doses of Ritonavir(r) plus Abacavir(ABC)/Lamivudine(3TC): COL100758," poster TUPEB080, 4th
International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention, 22-25 July 2007, Sydney, Australia
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