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Effect of atazanavir versus other protease inhibitor-containing antiretroviral therapy on endothelial function in HIV-infected persons: Randomized controlled trial
  1. Andreas J Flammer (andreas.flammer{at}usz.ch)
  1. Cardiovascular Centre, Cardiology, University Hospital, CH-8091 Zurich, Switzerland
    1. Nhung T. T. Vo
    1. Division of Infectious Diseases and Hospital Epidemiology, University Hospital, CH-8091 Zurich, Switzerland
      1. Bruno Ledergerber
      1. Division of Infectious Diseases and Hospital Epidemiology, University Hospital, CH-8091 Zurich, Switzerland
        1. Frank Hermann
        1. Cardiovascular Centre, Cardiology, University Hospital, CH-8091 Zurich, Switzerland
          1. Andrea Gämperli
          1. Division of Infectious Diseases and Hospital Epidemiology, University Hospital, CH-8091 Zurich, Switzerland
            1. Angela Huttner
            1. Division of Infectious Diseases and Hospital Epidemiology, University Hospital, CH-8091 Zurich, Switzerland
              1. John Evison
              1. Division of Infectious Diseases, University Hospital, CH-3010 Berne, Switzerland
                1. Iris Baumgartner
                1. Division of Angiology, University Hospital, CH-3010 Berne, Switzerland
                  1. Matthias Cavassini
                  1. Division of Infectious Disease, University Hospital, CH-1011 Lausanne, Switzerland
                    1. Daniel Hayoz
                    1. Division of Angiology, University Hospital, CH-1011 Lausanne, Switzerland
                      1. Kurt Quitzau
                      1. Cardiovascular Centre, Cardiology, University Hospital, CH-8091 Zurich, Switzerland
                        1. Martin Hersberger
                        1. Institute of Clinical Chemistry, University Hospital, CH-8091 Zurich, Switzerland
                          1. Isabella Sudano
                          1. Cardiovascular Centre, Cardiology, University Hospital, CH-8091 Zurich, Switzerland
                            1. Frank Ruschitzka
                            1. Cardiovascular Centre, Cardiology, University Hospital, CH-8091 Zurich, Switzerland
                              1. Thomas F. Lüscher
                              1. Cardiovascular Centre, Cardiology, University Hospital, CH-8091 Zurich, Switzerland
                                1. Georg Noll
                                1. Cardiovascular Centre, Cardiology, University Hospital, CH-8091 Zurich, Switzerland
                                  1. Rainer Weber (infweb{at}usz.uzh.ch)
                                  1. Division of Infectious Diseases and Hospital Epidemiology, University Hospital, CH-8091 Zurich, Switzerland

                                    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. We studied whether endothelial function improves after switching from other PI to atazanavir.

                                    Design: Randomized, 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 LDL-cholesterol >3mmol/L.

                                    Intervention: Patients were randomized either to continue the current PI or change to unboosted atazanavir.

                                    Main outcome measures: Endpoints at week 24 were endothelial function assessed by flow-mediated vasodilation (FMD) of the brachial artery, lipid profiles, high sensitive C-reactive protein, malondyaldehyde, total antioxidative capacity and oxidized LDL.

                                    Results: Baseline characteristics and mean FMD values of the two treatment groups were comparable (3.9±1.8% on atazanavir vs. 4.0±1.5% in controls). After 24 weeks’ treatment, FMD decreased to 3.3±1.4% and 3.4±1.7%, respectively (all p=n.s.). 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). HDL and triglyceride levels improved on atazanavir (p=0.03 and p=0.003, respectively) but not in the control group. Serum inflammatory and oxidative stress parameters did not change; oxidized LDL improved significantly in the atazanavir group.

                                    Conclusions: The switch from another PI to atazanavir among treatment experienced patients did not result in improvement of endothelial function despite significantly improved serum lipids. Not only atherogenic lipid profiles but also direct effects of reverse transcriptase inhibitor plus PI-containing combination on the endothelium may affect vascular function.

                                    ClinicalTrials.gov Identifier: NCT00447070

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