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Association of Abacavir and HIV Disease Factors with Endothelial Function in Patients on Long-Term Suppressive Antiretroviral Therapy
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Reported by Jules Levin
CROI 209 Montreal Feb 8-12
From ULES; this paper and an oral talk by Claudette Satchell on platelet hyper-reactivity & abacavir offer potential explanations for the association seen between abacavir and MIs.
Priscilla Y. Hsue, Yuaner Wu, Amanda Schnell, Peter Ganz, Peter Hunt, Hiroyu Hatano, Jeffrey N. Martin, and Steven G. Deeks
University of California, San Francisco
BACKGROUND
Recent studies suggest that HIV-infected patients are at increased risk for cardiovascular events. This may be due to both HIV disease-related factors (including inflammation) and treatment-related factors. Recently, exposure to 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 and is predictive of adverse cardiovascular outcomes including myocardial infarction, we investigated the association between both treatment- and disease-associated factors on endothelial function, focusing on patients responding to antiretroviral therapy. In particular, we performed an exploratory analysis of the association between current use of abacavir and endothelial function.
![Methods-1.gif](../images/031609/Methods-1.gif)
Statistical Analysis
Multivariable linear models were used to identify predictors of endothelial function. We adjusted for traditional cardiovascular risk factors and HIV disease characteristics including current CD4 count, nadir CD4 count, and duration of antiretroviral therapy.
RESULTS
We studied a total of 61 antiretroviral-treated patients with undetectable plasma HIV RNA levels. Overall, the median age of the HIV patients was 50 years, and ninety-five percent were male. The median duration of HIV infection was 18 years and the median duration of HAART was 8.6 years. Abacavir (ABC) was part of current treatment in half of the patients (n=30, 49%).
![HIV-2.gif](../images/031609/HIV-2.gif)
![Charac-3.gif](../images/031609/Charac-3.gif)
![FMD-4.gif](../images/031609/FMD-4.gif)
The median duration of ABC therapy was 1.2 years (IQR 0 to 6.8); Overall, the median FMD in all of the HIV patients was impaired (3.5%; IQR 2.3-5.6%). The FMD (endothelium-dependent) was more impaired in the abacavir-treated patients than those not on abacavir (2.8% vs. 4.9%, p=0.01). There was no difference in endothelium-independent FMD between the two groups. After adjustment for age, gender, traditional risk factors, HIV-specific factors, and baseline brachial artery diameter, current abacavir use was independently associated with lower FMD (Figure 1, p=0.02). Duration of HAART, duration of protease inhibitors, CD4 nadir, and proximal CD4 count were not associated with FMD. Current DDI or TFV use were also not associated with reduced FMD. Examples of FMD studies are shown in Figure 2.
CONCLUSIONS
Endothelial function, a central mechanism in atherosclerosis and a marker of cardiovascular risk, is impaired among long-term HAART-treated patients with undetectable viral loads. We did not find evidence for a strong relationship between CD4 nadir or current CD4 and FMD, although our power to detect small differences may have been limited. We also did not find a relationship between duration of HAART or use of protease inhibitors and FMD. Current use of abacavir was independently associated with impaired endothelial function in this cohort of long-term treated patients; this effect was not readily explained by measured confounders, including traditional risk factors. Further studies will need to determine if abacavir-associated changes in endothelial function contribute to the clinically observed relationship between abacavir use and myocardial infarction.
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