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The Effects of Intermittent, CD4-guided ART on Peripheral Limb Fat and Metabolic Parameters: The SMART Body Composition Substudy
Fehmida Visnegarwala*1,2, Fehmida Visnegarwala*1,2, B Grund3, A Thomas3, K Ellis1, C Gibert4, J Shlay5, F Drummond6, E Martinez7, W El-Sadr8, A Carr9, and Body Composition Sub-study Investigators of the SMART trial
1Baylor Coll of Med, Houston, TX, US; 2CPCRA; 3Univ of Minnesota, Minneapolis, US; 4VAMC, Washington, DC, US; 5Denver CPCRA, Denver Publ Hlth, Univ of Colorado Hlth Sci Ctr, US; 6Natl Ctr for HIV Epidemiology and Clin Res, Univ of New South Wales, Australia; 7Hosp Clin, Univ of Barcelona, Spain; 8Harlem Hosp, Columbia Univ, New York, NY, US; and 9St Vincent's Hosp, Univ New South Wales, Sydney, Australia
Background: Interruption of ART has been used in an attempt
to mitigate its body fat and atherogenic metabolic abnormalities. This has not
been assessed in a randomized trial. SMART randomized patients with CD4 counts
>350 cells/mm3 to intermittent, CD4-guided ART (stop ART >350
and start <250 cells/mm3) (drug conservation) or continuous ART
(viral suppression).
Methods: Participants from 32 sites in the United States, Australia,
and Spain
were co-enrolled in a body composition substudy. A key primary aim was to
evaluate peripheral limb fat mass and limb fat percent by annual DEXA. Fasting
(≥12 hours) lipid and glycemic parameters were done at months 4 and 8 and
annually. Statistical comparisons of randomized groups were adjusted for sex,
race, and baseline values.
Results: We randomized 142 and 133 patients to the drug
conservation, and viral suppression arms, respectively. At baseline, mean age
was 48 years, 19% were female, 26% were black, 22% had prior AIDS, 39% had
provider-reported lipoatrophy, 92% were ART-experienced (74% on ART at
baseline), and 8% naοve; median CD4 count was 562 cells/mm3 and 58%
had HIV RNA ≤400 copies/mL. Median baseline limb fat mass was 6.6 kg
(limb fat 8.4%), and mean total cholesterol was 190 mg/dL, HDL-C 40 mg/dL,
LDL-C 110 mg/dL, and triglycerides 226 mg/dL. At 12 months, 45% of patients in
drug conservation had
re-initiated ART. After 12 months, mean limb fat mass changes were +0.12 kg in
drug conservation and 0.14 kg in viral suppression (estimated difference 0.32
kg, 95%CI 0.19 to 0.85, p = 0.22, n = 213 patients), mean changes of 7.6%
and 0.5%, respectively (estimated difference 7.4%, 1.5 to 13.3%, p = 0.02). Mean changes in limb fat
percent were +0.2% and 0.2%, respectively (estimated difference, 0.5%, 0.0 to
0.9%, p = 0.03). Treatment difference
in limb fat change was similar for those on or off ART at baseline (p >0.4 for interaction, all 3
outcomes). There were significant reductions in lipids in drug conservation
relative to viral suppression starting at month 4. Month 4 lipid changes were (n = 165 patients): total cholesterol (estimated difference 36
mg/dL, 48 to 24, p <0.001),
LDL-C (estimated difference 16.9 mg/dL, 26.0 to 7.8, p <0.001); HDL-C (5.1 mg/dL, 8.0 to 2.1; p <0.001); triglycerides (68 mg/dL, 101 to 35, p <0.001). There was no significant
difference observed (n = 159) for
glucose, insulin or C-peptide at month 4.
Conclusions: Compared to continuous ART, use of intermittent,
CD4-guided ART modestly improved peripheral fat at 12 months, and resulted in
lower fasting lipid, but not glycemic, levels over 4 months.
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