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Peripheral and Visceral Fat Changes following a Treatment Switch to a Nonthymidine Analogue or Nucleoside-sparing Regimen in Patients with Peripheral Lipoatrophy: 48-week Final Results of ACTG A5110, a Prospective, Randomized Multicenter Clinical Trial
Robert Murphy*1, J Zhang2, R Hafner3, K Yarasheski4, K Tashima5, B Berzins1, S Owens6, A Shevitz7, S Evans2, P Tebas8, and ACTG A5110 Team
1Northwestern Univ Med Sch, Chicago, IL, US; 2Harvard Sch of Publ Hlth, Boston, MA, US; 3Div of AIDS, NIAID, NIH, DHHS, Bethesda, MD, US; 4Washington Univ, St Louis, MO, US; 5Brown Univ, Providence, RI, US; 6Frontier Sci & Tech Res Fndn, Amherst, NY, US; 7Tufts Univ Sch of Med, Boston, MA, US; and 8Univ of Pennsylvania, Philadelphia, US
Background: Options for patients with peripheral lipoatrophy are limited and include surgery and treatment
changes to less toxic ART. Switching the thymidine
analog to a nonthymidine analog or changing to a
nucleoside (NRTI)-sparing regimen has been shown to partially reverse peripheral
lipoatrophy after 24 weeks. We report 48-week
longitudinal data.
Methods: Patients
at 15 ACTG sites receiving thymidine analogs stavudine (d4T)- or zidovudine (ZDV)-containing regimens with HIV RNA viral
load of £500 c/mL and clinical evidence of peripheral lipoatrophy were
prospectively randomized to: switch
thymidine analog to abacavir
(ABC), or discontinue all ART and switch to lopinavir/r
(LPV/r) + nevirapine (NVP), a NRTI-sparing regimen,
or delay switching for 24 weeks. Centrally analyzed single-slice CT of
mid-thigh and abdominal fat, metabolic, and virologic
and immunologic parameters were measured at
baseline, week 24 and week 48 post-treatment intervention.
Results: Of the 101 patients
enrolled (85% men, 69% white), 77 switched immediately and 24 delayed. Median
age was 46 years, CD4 = 611 cells/mm3, viral load <200 copies/mL = 96%; 76% were on d4T and 24 % on ZDV. Baseline median
(IQR) subcutaneous thigh fat was 18.9 (8.3, 29.2) cm2, subcutaneou abdominal adipose tissue (SAT) 74.2 (44.6, 122.5)
cm2 , visceral adipose tissue (VAT) 116.3
(69.8, 176.8) cm2 and VAT:TAT (total adipose tissue) ratio 0.58
(0.45, 0.71). The table shows median percentage changes at 24 and 48 weeks: There
were significant subcutaneou thigh fat and SAT
increases over time and decreases in VAT:TAT for both interventions and a
decrease in VAT for ABC. There was a significant increase in CD4 for LPV/r +
NVP. LPV/r + NVP had a significantly shorter time to grade 3 or higher toxicity
(p = 0.007) but drop out rates were
similar for both interventions.
|
Treatment arm (n)
|
SQ thigh fat
|
SAT
|
VAT
|
VAT:TAT
|
CD4
|
Viral load
>500 copies
|
|
24 w
|
48 w
|
24 w
|
48 w
|
24 w
|
48 w
|
24 w
|
48 w
|
24 w
|
48 w
|
24 w
|
48 w
|
|
ABC (48)
|
2
|
18**
|
20**
|
29**
|
-14**
|
-15**
|
-10**
|
-14**
|
-3
|
-2
|
4
|
4
|
|
LPV/r+NVP (53)
|
8*
|
17**
|
17**
|
33**
|
-3
|
-4
|
-8**
|
-11**
|
10**
|
11**
|
6
|
4
|
|
Between arm p value
|
0.29
|
0.57
|
0.60
|
0.6
|
0.10
|
0.09
|
0.44
|
0.38
|
0.02
|
0.08
|
0.43
|
0.64
|
Within arm change
p £0.05*, p £0.01**.
Conclusions: Switching
d4T or ZDV to a nonthymidine analog or changing to a
NRTI-sparing regimen is associated with continuous and equivalent improvements
in thigh fat, SAT, and VAT:TAT to 48 weeks. ABC tended
to reduce VAT more and CD4 count increases were greater with LPV/r + NVP.
|
