940 
Changes in Body Composition Attributable to Lamivudine, Stavudine, Zidovudine, and Abacavir in HIV-infected Persons Initiating ART
Judith Shlay*1, S Sharma2, G Bartsch2, G Peng2, C Gibert3, C Grunfeld4, and the CPCRA and INSIGHT.
1Denver CPCRA, Denver Publ Hlth, CO, US; 2Univ of Minnesota, Minneapolis, US; 3Wide-Reaching AIDS Prgm, VAMC and George Washington Univ, Washington, DC, US; and 4VAMC and Univ of California, San Francisco, US
Background: The long-term effects of individual and
combination NRTI use on body composition have not been well defined.
Methods: In a substudy of a multicenter clinical
trial, body composition changes were examined in participants initiating ART
with 1of 4 NRTI combinations (stavudine [d4T]+lamivudine [3TC], zidovudine [ZDV]+3TC,
abacavir [ABC]+3TC, d4T+didanosine [ddI]) with protease inhibitor (PI), NNRTI,
or both. Midarm, midthigh, and waist subcutaneous tissue areas and waist
visceral tissue area were assessed at baseline and every 4 months. Rates of
change in body composition per year of exposure to combinations of and attributable
to the individual NRTI were calculated using 2 multivariate repeated measures
regression models: Model 1 used 4 variables with updated cumulative time
on each NRTI combination; Model 2 used 5 variables with updated cumulative time
on individual NRTI. All models adjusted for updated cumulative time on
individual PI, NNRTI, and baseline demographic and clinical parameters.
Results: Among 373 participants who met analysis
criteria, 66 received d4T+3TC, 199 received ZDV+3TC, 54 received ABC+3TC, and
54 received d4T+ddI at study entry. Median follow-up was 4 years. Estimated
rates of change per year of exposure are shown in the table. Rates for d4T+3TC
and ZDV+3TC for subcutaneous tissue area were less negative than for d4T or ZDV
alone. The positive rate of 3TC reduced the significant negative rates of d4T
and ZDV. For visceral tissue area the significant increase with 3TC combined
with the significant decrease with ABC resulted in a non-significant positive
rate for ABC+3TC. The increase in visceral tissue area with 3TC augmented the
slightly positive rates of ZDV and d4T significantly.
|
NRTI
|
Subcutaneous tissue area
(cm2/yr)(p)
|
Visceral tissue area
(cm2/yr)(p)
|
|
Combination:
|
Midarm
|
Midthigh
|
Waist
|
Waist
|
|
d4T+3TC
|
–0.92 (0.02)
|
–2.74 (<0.01)
|
–2.28 (0.19)
|
11.68 (<0.01)
|
|
ZDV+3TC
|
–1.45 (<0.01)
|
–1.97 (<0.01)
|
–2.20 (0.10)
|
14.84 (<0.01)
|
|
ABC+3TC
|
0.32 (0.40)
|
0.46 (0.53)
|
4.51 (<0.01)
|
2.59 (0.46)
|
|
d4T+ddI
|
–2.14 (<0.01)
|
–3.73 (<0.01)
|
–2.57 (0.19)
|
2.03 (0.63)
|
|
Individual:
|
|
|
|
|
|
d4T
|
–1.81 (<0.01)
|
–4.38 (<0.01)
|
–4.76 (<0.01)
|
0.97 (0.79)
|
|
ZDV
|
–2.47 (<0.01)
|
–3.69 (<0.01)
|
–5.74 (<0.01)
|
0.36 (0.92)
|
|
ABC
|
–0.52 (0.17)
|
–0.52 (0.58)
|
1.32 (0.41)
|
–11.5 (<0.01)
|
|
3TC
|
0.57 (0.20)
|
1.40 (0.10)
|
3.26 (0.09)
|
18.6 (<0.01)
|
|
ddI
|
–0.86 (0.09)
|
0.52 (0.58)
|
1.05 (0.62)
|
–0.56 (0.90)
|
Conclusions: In this prospective evaluation specific
differences were identified in the NRTI effects on body composition both
individually and in combination. For subcutaneous tissue area, the presence of
3TC reduced tissue loss associated with d4T and ZDV. For visceral tissue area,
when combined with d4T or ZDV, the tissue gain with 3TC remained while reducing
the visceral tissue loss associated with ABC. 3TC has a significant effect on body
composition.
|
