Effect of atazanavir versus other protease inhibitor-containing antiretroviral therapy on endothelial function in HIV-infected persons: randomised controlled trial
- A J Flammer1,
- N T T Vo2,
- B Ledergerber2,
- F Hermann1,
- A Gämperli2,
- A Huttner2,
- J Evison3,
- I Baumgartner4,
- M Cavassini5,
- D Hayoz6,
- K Quitzau1,
- M Hersberger7,
- I Sudano1,
- F Ruschitzka1,
- T F Lüscher1,
- G Noll1,
- R Weber2
- 1 Cardiovascular Centre, Cardiology, University Hospital Zurich, Zurich, Switzerland
- 2 Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland
- 3 Division of Infectious Diseases, University Hospital Bern, Bern, Switzerland
- 4 Division of Angiology, University Hospital Bern, Bern, Switzerland
- 5 Division of Infectious Diseases, University Hospital Lausanne, Lausanne, Switzerland
- 6 Division of Angiology, University Hospital Lausanne, Lausanne, Switzerland
- 7 Institute of Clinical Chemistry, University Hospital Zurich, Zurich, Switzerland
- Professor R Weber, Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Raemistrasse 100, CH-8091 Zurich, Switzerland; Rainer.Weber{at}usz.ch
- Accepted 24 June 2008
- Published Online First 24 July 2008
Abstract
Objective: Impaired endothelial function was demonstrated in HIV-infected persons on protease inhibitor (PI)-containing antiretroviral therapy, probably due to altered lipid metabolism. Atazanavir is a PI causing less atherogenic lipoprotein changes. This study determined whether endothelial function improves after switching from other PI to atazanavir.
Design: Randomised, observer-blind, treatment-controlled trial.
Setting: Three university-based outpatient clinics.
Patients: 39 HIV-infected persons with suppressed viral replication on PI-containing regimens and fasting low-density lipoprotein (LDL)-cholesterol greater than 3 mmol/l.
Intervention: Patients were randomly assigned to continue the current PI or change to unboosted atazanavir.
Main Outcome Measures: Endpoints at week 24 were endothelial function assessed by flow-mediated dilation (FMD) of the brachial artery, lipid profiles and serum inflammation and oxidative stress parameters.
Results: Baseline characteristics and mean FMD values of the two treatment groups were comparable (3.9% (SD 1.8) on atazanavir versus 4.0% (SD 1.5) in controls). After 24 weeks’ treatment, FMD decreased to 3.3% (SD 1.4) and 3.4% (SD 1.7), respectively (all p = ns). Total cholesterol improved in both groups (p<0.0001 and p = 0.01, respectively) but changes were more pronounced on atazanavir (p = 0.05, changes between groups). High-density lipoprotein and triglyceride levels improved on atazanavir (p = 0.03 and p = 0.003, respectively) but not in controls. Serum inflammatory and oxidative stress parameters did not change; oxidised LDL improved significantly in the atazanavir group.
Conclusions: The switch from another PI to atazanavir in treatment-experienced patients did not result in improvement of endothelial function despite significantly improved serum lipids. Atherogenic lipid profiles and direct effects of antiretroviral drugs on the endothelium may affect vascular function.
Trial registration number: NCT00447070.
Footnotes
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Funding: This work was supported by the Swiss National Research Foundation (SNF) grant no 32000BO-105758 to FR and grant no 32000B0–100318 to GN, the Foundation for Cardiovascular Research, Zurich, Switzerland and an unrestricted educational grant from Bristol-Myers-Squibb, Switzerland.
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Competing interests: RW has received travel grants or speakers honoraria from Abbott, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Merck Sharp & Dome, Pfizer, Roche, TRB Chemedica and Tibotec. BL has received travel grants or honoraria from Abbott, Aventis, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Merck Sharp & Dome, Roche and Tibotec. TFL and KQ have received grants for the conduct of clinical studies from Bristol-Myers Squibb.
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Ethics approval: The local ethics committees of the three university hospitals approved the study protocol and all procedures were in accordance with institutional guidelines and the Declaration of Helsinki.
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Patient consent: Obtained.
