Association of abacavir and impaired endothelial function in treated and suppressed HIV-infected patients.
BACKGROUND
HIV-infected patients have accelerated atherosclerosis. Abacavir has been associated with increased risk of cardiovascular events, for reasons that remain to be elucidated. As endothelial dysfunction is central to the pathogenesis of atherosclerosis, we tested the hypothesis that current treatment with abacavir is associated with impaired endothelial function.


METHODS
We studied a cohort of 61 antiretroviral-treated patients who had undetectable plasma HIV RNA levels. Endothelial function was assessed by measuring flow-mediated dilation (FMD) of the brachial artery. We compared FMD in patients treated with or without abacavir, while adjusting for traditional risk factors and HIV-specific characteristics.


RESULTS
The median age was 50 years (interquartile range 45-57). The median duration of HIV infection was 18 years, and the median CD4 cell count was 369 cells/microl. Thirty patients (49%) were receiving abacavir. Overall, the median FMD in the HIV-infected patients was low (3.5%; interquartile range 2.3-5.6%). The FMD was lower in the abacavir-treated patients than those not on abacavir (2.8 vs. 4.9%, P = 0.01). After adjustment for traditional risk factors, HIV-specific factors, and baseline brachial artery diameter, current abacavir use was independently associated with lower FMD (P = 0.017). Duration of therapy and CD4 cell count were not associated with reduced FMD.


CONCLUSIONS
Endothelial function, a central mechanism in atherosclerosis and a marker of cardiovascular risk, is impaired among antiretroviral-treated patients with undetectable viral loads. Current use of abacavir was independently associated with impaired endothelial function. This finding suggests that abnormal endothelial function may underlie the clinically observed increased risk in myocardial infarction among abacavir-treated patients.
Hsue
Priscilla Y
PY
Division of Cardiology, Positive Health Program of the Department of Medicine, San Francisco General Hospital, University of California-San Francisco, 1001 Potrero Avenue, San Francisco, CA 94110, USA. phsue@medsfgh.ucsf.edu
Hunt
Peter W
PW
Wu
Yuaner
Y
Schnell
Amanda
A
Ho
Jennifer E
JE
Hatano
Hiroyu
H
Xie
Yu
Y
Martin
Jeffrey N
JN
Ganz
Peter
P
Deeks
Steven G
SG
D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D015224:Dideoxynucleosides / Q000494:pharmacology* / Q000627:therapeutic use; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000503:physiopathology* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects; D019562:Viral Load; D000099227:Abacavir
D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D000099227:Abacavir