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Improvement in Facial & Limb Lipoatrophy at 48 Wks After Switch to Abacavir or Tenofovir
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Reported by Jules Levin
Intl AIDS Conference
Rio de Janeiro
July 24-27, 2005
This poster abstract looked at the Rave Study which took 47 patients with lipoatrophy who were taking AZT or d4T, and switched them to tenofovir or abacavir. After 48 weeks 3-D laser scan of the face was used to evaluate changes in facial fat and found improvements. Limb fat was measured at 48 weeks by DEXA, and found improvements. Changes in facial cheek fat volume correlated significantly with increases in limb fat shown by DEXA.
Today Wednesday is the last day of the conference in Rio, and of note are two oral Late Breakers on TMC114/r (PI) and Reverset (NRTI), both drugs are for persons with extensive drug resistance. As well, there will be an oral Late Breaker that appears interesting on drug resistant transmission.
"Improvements in facial lipoatrophy at 48 weeks following substitution of a thymidine analogue with tenofovir (TDF) or abacavir (ABC): a randomized, open-label study in persons with lipoatrophy and virologic suppression on HAART"
P Benn1, V Sauret2, J Cartledge1, C Ruff2, CA Sabin3, G Moyle4, R Richards2, G Reilly5, SG Edwards1
Depts of GUM, Camden PCT1, Medical Physics, University College Hospital2, Primary Care Population Sciences, RFUCLMS3, Chelsea & Westminster Hospital4, and Gilead Sciences5, UK
BACKGROUND
Thymidine analogue therapy is associated with peripheral fat loss and lipoatrophy. Switching to either TDF or ABC has been shown to lead to improvements in limb fat. Few data exist on the impact of switching therapy on the severity of facial lipoatrophy.
OBJECTIVES
To compare changes in facial contour with limb fat recovery in individuals using TDF or ABC as substitutes for a thymidine analogue.
STUDY DESIGN
We conducted a sub-study in 47 individuals recruited to RAVE; an open-label randomized study in 105 patients on AZT or d4T who substituted either TDF 300mg QD or ABC 300mg BID for the thymidine analogue. All individuals were stable on ARV therapy for >24/52 with a viral load <400 c/ml x 2 consecutive and most recent VL <50 c/ml and all had evidence of lipodystrophy. Individuals also underwent surface laser imaging of face at baseline and 48 weeks.
METHODS
3-D surface laser assessment of the face has been used by plastic and maxillo-facial surgeons to evaluate the outcome of surgery. It is quick and easy to perform, non-invasive and relatively inexpensive costing 50 UK pounds, US $79, Euro 75 per scan (June 2005).
SCANNER
The authors showed a picture in the poster of a patient sitting in a chair opposite a laser. A thin vertical line of light shone over the face as the person rotates. The light is reflected from the rotating face by two pairs of mirrors into a digital camers. Thus, producing a 3-D image of the face.
By aligning bony landmarks it is possible to superimpose these images; the difference (millimeters) between the scans was demonstrated by pictures on the poster. The 3-D laser facial scans at baseline and week 48 were then superimposed using bony landmarks. Areas overlying the forehead and both cheeks were compared. The variation between scans were calculated using the net volume difference (mm3) of each of these three areas.
Associations between the facial imaging parameters and other measures of body composition at 48 weeks were measured using Spearman's rank correlation.
RESULTS
Volume Change (mm3) at week 48 overlying forehead and cheeks
Forehead:
-189 (TDF)
-101 (ABC)
p=0.41
NOTE: authors told me there is no fat on forehead so you would not expect to see change.
Left Cheek:
+1343 (TDF)
+1031 (ABC)
Right Cheek:
+1489 (TDF)
+1175 (ABC)
Total Cheek:
+2812 (TDF)
+2208 (ABC)
p=0.88
*reproducibility: mean volume difference (mm3) between two scans one week apart in 17 HIV positive men with varying degrees of facial lipoatrophy.
**collagen: mean volume difference (mm3) between two scans before and after 19 HIV positive men underwent collagen injections into the cheeks.
#the mean volume increase overlying the cheeks was greater in those reporting no change or an improvement in their facial lipoatrophy (3387 mm3, n=28) compared to those with progression (841 mm3, n=14), however this is not significant (p=0.19).
Median Change in Limb Fat at 48 Weeks for all Rave Study and Sub-study Patients (DEXA arm fat + total leg fat in grams)
TDF overall=52 TDF substudy=23
ABC overall=52 ABC substudy=24
Week 24:
+200 TDF
+200 ABC
Week 48:
+390 TDF overall group
+349 TDF substudy group
+300 ABC overall
+422 ABC substudy
Change in Limb Fat over 48 weeks plotted against total cheek volume difference at 48 weeks
There was a plot on the poster. And authors report there was a significant correlation between mean total change in limb fat and total change in cheek volume (mm3) as shown in plot. After excluding individuals who had received steroids (n=1) and NewFill injections into the cheeks (n=2) during the study period the adjusted Spearman's rank coefficient is 0.35 (p=0.03).
CONCLUSIONS BY AUTHORS
--substitution of thymidine analogues in individuals with lipoatrophy with either TDF or ABC results in improvements in facial lipoatrophy as measured by surface laser scans
--as replacements for thymidine analogues in persons with lipoatrophy, TDF and ABC similarly restore limb fat over 48 weeks.
--changes in facial cheek volume significantly correlate with increases in limb fat shown by DEXA.
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