Effect of atazanavir versus other protease inhibitor-containing antiretroviral therapy on endothelial function in HIV-infected persons: randomised controlled trial.
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.


METHODS
Randomised, observer-blind, treatment-controlled trial.


METHODS
Three university-based outpatient clinics.


METHODS
39 HIV-infected persons with suppressed viral replication on PI-containing regimens and fasting low-density lipoprotein (LDL)-cholesterol greater than 3 mmol/l.


METHODS
Patients were randomly assigned to continue the current PI or change to unboosted atazanavir.


METHODS
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.


BACKGROUND
NCT00447070.
Flammer
A J
AJ
Cardiovascular Centre, Cardiology, University Hospital Zurich, Zurich, Switzerland.
Vo
N T T
NT
Ledergerber
B
B
Hermann
F
F
Gämperli
A
A
Huttner
A
A
Evison
J
J
Baumgartner
I
I
Cavassini
M
M
Hayoz
D
D
Quitzau
K
K
Hersberger
M
M
Sudano
I
I
Ruschitzka
F
F
Lüscher
T F
TF
Noll
G
G
Weber
R
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D000069446:Atazanavir Sulfate; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1; D006801:Humans; D008055:Lipids / Q000097:blood; D008099:Liver / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D011446:Prospective Studies; D011725:Pyridines / Q000627:therapeutic use*; D055815:Young Adult
D017320:HIV Protease Inhibitors; D008055:Lipids; D009842:Oligopeptides; D011725:Pyridines; D000069446:Atazanavir Sulfate