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  XVII International AIDS Conference
Mexico City
3-8 August 2008
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Switch to Atazanavir/Ritonavir Does Not Trim Trunk Fat in 48 Weeks
  XVII International AIDS Conference
August 3-8, 2008
Mexico City
Mark Mascolini
Switching from a twice-daily ritonavir-boosted protease inhibitor (PI) to once-daily atazanavir/ritonavir had no impact on trunk-to-limb-fat ratio by week 48, the primary endpoint of the REAL study [1]. Nor did shifting to atazanavir significantly change most other body fat measures in 48 weeks. Certain lipid levels improved significantly after patients traded other PIs for atazanavir/ritonavir, but these changes had little apparent clinical impact during the study.
REAL randomized 131 people to substitute once-daily atazanavir/ritonavir for a twice-daily ritonavir-boosted PI and 69 to continue their current regimen. Everyone had a viral load below 400 copies and a waist circumference wider than 90 cm. Graeme Moyle (Chelsea and Westminster Hospital, London) and REAL colleagues used DEXA scans to measure trunk and limb fat and CT scans to gauge visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and total adipose tissue (TAT).
Viral rebound rates from below to above 50 copies through week 48 were equivalent in the two study groups, 5% with atazanavir/ritonavir and 6% with the continued PIs. People who stayed with their original boosted PI did gain more CD4 cells over 48 weeks, averaging 44 more cells versus 14.5 more with atazanavir/ritonavir, but that difference fell short of statistical significance (P = 0.2).
After 48 weeks the REAL team saw no significant difference between regimens in percent change in trunk-to-limb-fat ratio: +0.02% with atazanavir/ritonavir versus -0.02% with continued PI, a nonsignificant difference (P = 0.48). Switching a twice-daily boosted PI to once-daily atazanavir/ritonavir did not significantly change VAT, SAT, VAT-to-TAT ratio, or VAT-to-SAT ratio. People starting atazanavir/ritonavir did gain more total body fat than those sticking with their original PIs (+2.1% versus -2.2%, P = 0.00385).
REAL participants who swapped their twice-daily boosted PI for atazanavir/ritonavir enjoyed significant improvements over the continued-PI control group in several fasting lipid measures calculated as percent change from baseline for atazanavir versus the control PI group:
- Total cholesterol: -12.1%, P < 0.0001
- Low-density lipoprotein (LDL or "bad") cholesterol: -12.6%, P = 0.0086
- Triglycerides: -13.7%, P = 0.0411
- Non-high-density lipoprotein cholesterol: -14.3%, P < 0.0001
- Apolipoprotein B (a component of LDL cholesterol): -8.6%, P = 0.0061
Still, only LDL cholesterol and apolipoprotein B (an atherosclerosis predictor) rose in the PI control group. One person stopped a control PI because of high triglycerides and 1 because of squamous cell carcinoma for a discontinuation rate of 3%. Five people (3%) switching to atazanavir/ritonavir dropped that regimen because of treatment-related side effects--high bilirubin in 3, jaundice in 1, and Stevens-Johnson syndrome in 1. Four people (3%) had serious adverse events while taking atazanavir/ritonavir, versus none in the control group. Moyle and coworkers speculated that the significant lipid improvements seen with atazanavir did not translate into significant body fat changes because fat abnormalities take longer than 48 weeks to turn around after swapping another PI for atazanavir. A randomized study of people trading zidovudine/lamivudine for tenofovir/emtricitabine, detailed in a poster next to Moyle's [2], showed that this nucleoside swap can promote significant limb fat gains in 24 weeks in people with less than 7.1 kg of limb fat at study entry. Follow-up will continue in REAL though 96 weeks.
1. Moyle G, Girard JM, Andrade J, et al. Continuation of BID boosted PI vs switch to once-daily ATV/RTV for the management of lipodystrophy: 48 week primary analysis of the 96 week multicenter, open-label, randomized, prospective REAL study. XVII International AIDS Conference. August 3-8, 2008. Mexico City. Abstract MOPDB103.
2. Martinez E, Ribera E, Pulido F, et al. Early improvement of limb fat content in patients switching from AZT/3TC to FTC/TDF (TVD): a 24 week interim analysis of the RECOMB trial. XVII International AIDS Conference. August 3-8, 2008. Mexico City. Abstract MOPDB102.