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Abacavir (Ziagen) May Contribute to Impaired Endothelial Function in HIV Patients with Suppressed Viral Load

Abacavir (Ziagen, also in the Epzicom and Trizivir combination pills) may interfere with endothelial function, or normal working of blood vessel linings, impairing blood flow and possibly contributing to the increased risk of cardiovascular events observed in some studies, according to a report in the September 24, 2009 issue of AIDS.

By Liz Highleyman

Recent studies have produced conflicting data regarding the effect of abacavir on cardiovascular outcomes. The large D:A:D study and the SMART treatment interruption trial showed that patients currently taking abacavir-containing regimens were more likely to experience heart attacks and other cardiovascular events.

However, a meta-analysis of more than 50 studies conducted by abacavir manufacturer GlaxoSmithKline did not find such an association, and more recent research suggests that confounding factors such as kidney disease may explain the link.

The mechanism by which abacavir might contribute to heart problems is unclear, since it does not cause the type of blood lipid abnormalities associated with some other antiretroviral drugs. But, according to the new report in AIDS, it may have an effect on blood vessel function.

Priscilla Hsue from the Positive Health Program at San Francisco General Hospital and colleagues tested the hypothesis that current treatment with abacavir is associated with impaired endothelial function.

The study looked at a cohort of 61 HIV patients on stable antiretroviral therapy (ART) for at least 6 months who had undetectable plasma viral load. Most (95%) were men, the median age was 50 years, the median duration of HIV infection was 18 years, and the median CD4 count was 369 cells/mm3. About half the patients (n = 30) were taking abacavir.

Endothelial function was assessed using flow-mediated dilation (FMD) of the brachial artery in the upper arm, a measure of how well blood vessels respond to changes in blood flow. The investigators compared FMD in patients treated with or without abacavir, adjusting for traditional risk factors (e.g., older age, high blood pressure, smoking) and HIV-related characteristics.

Results

Overall, median FMD in the HIV positive patients regardless of type of ART was low (3.5%), indicating impaired blood vessel function and poorer blood flow.
FMD was significantly lower, however, in the current abacavir-treated group compared with patients not taking abacavir (2.8% vs 4.9%; P = 0.01).
Among 5 patients who had taken abacavir in the past, FMD was also lower compared to those with no prior history of abacavir use (P = 0.04).
After adjusting for traditional risk factors, HIV-specific factors, and baseline brachial artery diameter, current abacavir use remained independently associated with lower FMD (P = 0.017).
Duration of ART and CD4 count were not associated with reduced FMD.

Based on these findings, the study authors concluded, "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," they continued. "This finding suggests that abnormal endothelial function may underlie the clinically observed increased risk in myocardial infarction among abacavir-treated patients."

Further research is needed to confirm these findings in a larger patient population, and to shed light on the mechanisms by which abacavir might impair blood vessel function. A growing body of research indicates that chronic inflammation contributes to non-AIDS illnesses such as heart disease in people with HIV. Studies have produced mixed data, however, about whether abacavir is associated with changes in markers of inflammation.

Division of Cardiology, Positive Health Program of the Department of Medicine, San Francisco General Hospital, University of California at San Francisco, San Francisco, CA.

10/23/09

Reference
P Hsue, PW Hunt, Y Wu, and others. Association of abacavir and impaired endothelial function in treated and suppressed HIV-infected patients. AIDS 23(15): 2021-2027. September 24, 2009. (Abstract).