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Endothelial Function, Inflammatory Markers Do Not Change 24 Weeks After Switch to Atazanavir
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16th Conference on Retroviruses and Opportunistic Infections,
February 8-11, 2009, Montreal
Mark Mascolini
Total cholesterol and triglycerides fell significantly when hyperlipidemic people switched from a boosted protease inhibitor (PI), usually lopinavir, to atazanavir/ritonavir [1]. But 24 weeks after the switch, endothelial function and cardiovascular inflammatory markers had not changed significantly in people who started atazanavir or people who stayed with their original PI. Robert Murphy and colleagues in the US, Argentina, and Italy did not speculate on the clinical implications of their findings. (from Jules: perhaps HIV causes endothelial dysfunction that may not be reversible by a switch to a more friendly lipid ART medication).
Murphy and coworkers randomized 50 people taking a stable ritonavir-boosted PI regimen to continue their drugs or to swap the PI for 300/100 mg of atazanavir/ritonavir once daily. Everyone had a viral load below 500 copies and a fasting low-density lipoprotein (LDL) cholesterol level above 130 mg/dL or triglycerides above 200 mg/dL. The study excluded anyone taking a nonnucleoside, anyone with cardiovascular disease or diabetes, or anyone who smoked more than one pack of cigarettes daily. However, 42% of study participants did smoke. The investigators also excluded anyone who began lipid-lowering therapy within 4 weeks and anyone who used systemic immunomodulators, insulin-sensitizing drugs, or many vitamin supplements.
Before the switch and at weeks 12 and 24, the researchers measured flow-mediated vasodilation to gauge endothelial function. They also measured lipoproteins, numerous cardiovascular inflammatory markers, and insulin and glucose metabolism. The primary endpoint was change in brachial artery flow-mediated vasodilation from baseline to week 24.
The two groups matched closely in age (median 43 with atazanavir and 42.5 with a continued PI), gender (85% and 83% male), race (69% and 63% white), current smoking (39% and 46%), and current lipid-lowering therapy (31% and 29%). Time on antiretroviral therapy was longer in the atazanavir group (10 versus 6 years). Most enrollees, 80%, were taking lopinavir/ritonavir.
Viral load, CD4 count, blood pressure, body mass index, lipid values, cardiovascular inflammatory markers, bilirubin, and various insulin and glucose measures did not differ significantly between the 26 people randomized to atazanavir and the 24 who kept their current PI. Median total cholesterol stood at 204 mg/dL in both groups, LDL cholesterol at 126.5 mg/dL in the switch group and 127 mg/dL in controls, high-density lipoprotein (HDL) cholesterol at 37 and 40.5 mg/dL, triglycerides at 244 and 203 mg/dL (P = 0.562), and total-to-HDL cholesterol ratio at 4.77 and 4.58.
Flow-mediated vasodilation at 24 weeks did not differ from baseline or between the two groups, even after adjustment for changes in brachial artery diameter:
• Flow-mediated vasodilation (%): 5.31 atazanavir, 5.77 control, P = 0.534
• Flow-mediated dilation absolute change from baseline: -1.14 atazanavir, +0.25 control, P = 0.601
Nor did the two groups differ at week 24 in glucose, insulin, insulin resistance, or any inflammation marker, including high-sensitivity C-reactive protein, D-dimer, interleukin 10, or tumor necrosis factor r2. Total cholesterol, triglycerides, and non-HDL cholesterol did improve significantly in a 24-week comparison between atazanavir and the continued-PI arm. Total bilirubin rose significantly with atazanavir.
Reference
1. Murphy R, Zala C, Berzins B, et al. Endothelial function, lipoproteins, and cardiovascular inflammatory markers in treated HIV-infected patients with hyperlipidemia who were switched to an atazanavir-containing regimen or continued on other PI-based therapy: switch to atazanavir and brachial artery reactivity study. 16th Conference on Retroviruses and Opportunistic Infections. February 8-11, 2009. Montreal. Abstract 722.
(This poster is online at http://www.retroconference.org/2009/PDFs/722.pdf
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