Abacavir impairs endothelial function, possibly explaining increased heart attack risk

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Treatment with abacavir impairs endothelial function, providing a possible explanation for the drug’s association with an increased risk of heart attack, US investigators report in the September 24th edition of AIDS.

They found that patients currently receiving abacavir (as well as those who had taken the drug in the past) had impaired flow-mediated dilation in the brachial artery compared to individuals with no history of treatment with the drug.

Patients with HIV have an increased risk of cardiovascular disease. A number of reasons have been suggested for this including inflammation, the effects of HIV, and the side-effects of antiretroviral drugs.

Glossary

cardiovascular

Relating to the heart and blood vessels.

myocardial infarction

Heart attack. Myocardial refers to the muscular tissue of the heart. An infarction is the obstruction of the blood supply to an organ or region of tissue.

inflammation

The general term for the body’s response to injury, including injury by an infection. The acute phase (with fever, swollen glands, sore throat, headaches, etc.) is a sign that the immune system has been triggered by a signal announcing the infection. But chronic (or persisting) inflammation, even at low grade, is problematic, as it is associated in the long term to many conditions such as heart disease or cancer. The best treatment of HIV-inflammation is antiretroviral therapy.

cardiovascular disease

Disease of the heart or blood vessels, such as heart attack (myocardial infarction) and stroke.

diabetes

A group of diseases characterized by high levels of blood sugar (glucose). Type 1 diabetes occurs when the body fails to produce insulin, which is a hormone that regulates blood sugar. Type 2 diabetes occurs when the body either does not produce enough insulin or does not use insulin normally (insulin resistance). Common symptoms of diabetes include frequent urination, unusual thirst and extreme hunger. Some antiretroviral drugs may increase the risk of type 2 diabetes.

Some studies have recently found an association between treatment with abacavir (Ziagen, also in the combination pills Kivexa and Trizivir) and heart attack. The reasons for this are not understood. However, it has been suggested that therapy with the drug is associated with impaired endothelial function, an established predictor of cardiovascular disease.

Measuring flow mediated dilation in the brachial artery can predict which patients have a future risk of cardiovascular disease. This measurement can change rapidly in response to the use of anti-HIV drugs, and is sensitive to inflammation. Investigators involved in the Study of the Consequences of the Protease Inhibitor Era (SCOPE) cohort therefore performed a study to see if flow mediated dilation of the brachial artery was impaired in HIV-positive individuals with a history of treatment with abacavir.

A total of 61 individuals were involved in the study. All had been taking stable antiretroviral therapy for at least six months and had a viral load below 75 copies/ml. The patients had been infected with HIV for a median of 18 years, and their median CD4 cell count was 369 cells/mm3. The median age of these patients was 50 years and 95% were men. Abacavir was currently being taken by 30 patients, and the median duration of therapy with the drug was a little over one year.

Results showed that endothelium function was impaired in the cohort, with median flow mediated dilation of the brachial artery being 3.5%.

However, this flow mediated dilation was significantly more impaired in patients taking abacavir than it was in individuals who were not receiving this drug (2.8% vs 4.9%, p = 0.01).

Five patients had a previous history of treatment with abacavir, and these individuals had significantly poorer flow mediated dilation than those who had never taken abacavir (p = 0.04).

The association between abacavir treatment and impaired endothelial function remained significant after the investigators took into account traditional risk factors for cardiovascular disease such as family history, diabetes, high blood pressure and high lipids.

“Our study may help provide a biological mechanism for the association between myocardial infarction and recent or current abacavir use seen in observational studies”, comment the investigators. They add, “future studies will need to confirm our findings and to help determine if abacavir-associated impairment in endothelial function contributes to the clinically observed relationship between current abacavir use and myocardial infarction.”

References

Hsue PY et al. Association of abacavir and impaired endothelial function in treated and suppressed HIV-infected patients. AIDS 23: 2021-2027, 2009.

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