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Body composition changes on Darunavir/Ritonavir (DRV/r) + either Raltegravir (RAL) or Tenofovir/Emtricitabine (TDF/FTC) as first-line antiretroviral therapy. NEAT 001/ANRS 143. Body composition sub-study.......Bigger Trunk Fat Gains With Raltegravir Than TDF/FTC (Both With DRV/r)
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Conference on Retroviruses and Opportunistic Infections (CROI), February 22-25, 2016, Boston
Mark Mascolini
WEBCAST link: http://www.croiwebcasts.org/console/player/29446?mediaType=audio&
People randomized to raltegravir plus darunavir/ritonavir (DRV/r) gained more trunk fat through 96 weeks than those randomized to tenofovir/emtricitabine (TDF/FTC) plus DRV/r in the NEAT001/ANRS143 trial [1]. Limb fat changes did not differ significantly between the two study arms at 96 weeks.
Because few studies compare fat changes in nucleoside-sparing versus nucleoside-containing regimens, NEAT investigators made this comparison of a randomly selected subgroup representing the two study arms. Antiretroviral-naive participants took standard doses of raltegravir, TDF/FTC, and DRV/r. Researchers assessed fat changes by DXA scans at baseline, week 48, and week 96. In the original trial, the raltegravir arm proved virologically noninferior to the TDF/FTC arm at 96 weeks, but the failure rate was higher with raltegravir/DRV/r in people with a high pretreatment viral load or low CD4 count [2].
The analysis included 61 people randomized to raltegravir and 65 randomized to TDF/FTC. Median age stood at 40, 90.5% of participants were men, and 82% were white. The two groups did not differ much in body mass index, waist circumference, hip circumference, or waist-to-hip ratio. Total body fat mass was significantly lower in the raltegravir group at baseline (median 14.3 versus 17.1 kg, P = 0.014), but the groups did not differ in baseline limb fat, trunk fat mass, trunk lean mass, or total body lean mass.
Through 48 weeks people in the raltegravir arm gained more limb fat mass than those in the TDF/FTC arm (mean change 20.4% versus 11.6%), but the difference fell well short of statistical significance (P = 0.25). At week 96 the difference was even smaller (mean change 9.8% versus 4.9%, P = 0.44).
Trunk fat mass rose substantially through 48 weeks in both the raltegravir group and the TDF/FTC group (mean change 12.2% and 13.8%), and that difference lacked significance. But over the following 48 weeks, people taking raltegravir continued to gain trunk fat while people taking TDF/FTC lost some trunk fat. As a result, the mean change at week 96 was significant (24.3% versus 9.8%, P = 0.049). Change in total body fat mass tended to be greater with raltegravir than with TDF/FTC at week 48 (mean change 20.4% versus 11.3%, P = 0.11) and at week 96 (mean change 15.8% versus 6.0%, P = 0.11). The study groups did not differ significantly in mean change in total body lean mass at 48 or 96 weeks.
Baseline insulin and leptin levels correlated positively with limb fat and trunk fat. After statistical adjustment, every 10% gain in leptin from baseline through week 48 correlated with a 0.5% increase in limb fat mass at week 48 (P < 0.001) and a 0.5% increase in total body fat mass at week 48 (P < 0.001). Change in insulin through 48 weeks did not correlate with these two fat changes. A 10% rise in leptin at week 48 also correlated with greater limb fat mass, trunk fat mass, and total body fat mass at week 96, and a 10% gain in insulin through 48 weeks correlated with higher total body fat mass at week 96. These correlations held true independently or treatment arm.
References
1. Bernardino JJ, Mocroft A, Cedrick Wallet C, et al. Body composition changes on DRV/r + either RAL or TDF/FTC as first-line ART. Conference on Retroviruses and Opportunistic Infections (CROI), February 22-25, 2016, Boston. Abstract 45.
2. Raffi F, Babiker AG, Richert L, et al. First-line RAL + DRV/r is non-inferior to TDF/FTC + DRV/r: The NEAT001/ANRS143 randomised trial. Conference on Retroviruses and Opportunistic Infections. March 3-6, 2014, Boston. Abstract 84LB. http://www.natap.org/2014/CROI/croi_29.htm
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