Change to atazanavir/ritonavir treatment improves lipids but not endothelial function in patients on stable antiretroviral therapy.
OBJECTIVE
Protease inhibitors and other antiretroviral drugs have been associated with dyslipidemia, endothelial dysfunction, and increased cardiovascular disease risk. The protease inhibitor atazanavir has an advantageous lipid profile; we studied its effects on arterial function and other metabolic and inflammatory cardiovascular disease risk factors.


METHODS
Prospective, randomized, multinational trial in HIV-infected patients receiving stable protease inhibitor-based therapy with plasma HIV RNA less than 500 copies/ml and fasting low-density lipoprotein cholesterol more than 130 mg/dl, or triglycerides more than 200 mg/dl.


METHODS
Patients were randomized to continue their current protease inhibitor or switch the protease inhibitor to atazanavir and continue ritonavir if given as a protease inhibitor booster for 24 weeks. Brachial artery flow-mediated dilation, lipoproteins, and inflammatory and metabolic markers were measured at baseline, week 12, and week 24. Median changes within (signed rank test) and between (Wilcoxon test) arms were calculated.


RESULTS
Twenty-six patients switched to atazanavir (all continued on ritonavir); 24 remained on their protease inhibitor regimen. Median CD4 cell count was 499 cells/mul, total cholesterol 204 mg/dl, low-density lipoprotein cholesterol 122 mg/dl, and triglycerides 244 mg/dl. There were no significant changes in flow-mediated dilation after 12 and 24 weeks. At 24 weeks, significant changes in the atazanavir vs. continued protease inhibitor group were observed for total cholesterol (-25 vs. +1.5 mg/dl, P = 0.009), triglycerides (-58 vs. +3.5 mg/dl, P = 0.013), and nonhigh-density lipoprotein cholesterol (-27 vs. -0.5 mg/dl, P = 0.014).


CONCLUSIONS
In dyslipidemic individuals with suppressed HIV RNA on stable therapy, changing the protease inhibitor to atazanavir/ritonavir for 24 weeks improved lipids; however, endothelial function, inflammatory, and metabolic markers did not change.
Murphy
Robert L
RL
Northwestern University Center for Global Health, Northwestern University, Chicago, Illinois 60611, USA. r-murphy@northwestern.edu
Berzins
Baiba
B
Zala
Carlos
C
Fichtenbaum
Carl
C
Dube
Michael P
MP
Guaraldi
Giovanni
G
Torriani
Francesca
F
Belsey
Elizabeth
E
Mitchell
Carol
C
Stein
James H
JH
D000328:Adult; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active; D000069446:Atazanavir Sulfate; D018791:CD4 Lymphocyte Count; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008055:Lipids; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage* / Q000009:adverse effects; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects; D019438:Ritonavir / Q000008:administration & dosage* / Q000009:adverse effects
D017320:HIV Protease Inhibitors; D008055:Lipids; D009842:Oligopeptides; D011725:Pyridines; D000069446:Atazanavir Sulfate; D019438:Ritonavir