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AIDS 2012: Aspirin Dampens Immune Activation in HIV+ People on ART

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Taking a daily aspirin reduces immune activation and activity of platelets -- the cells responsible for blood clotting -- which may help counteract the increased risk of cardiovascular problems among people with HIV taking antiretroviral therapy (ART), researchers reported at the XIX International AIDS Conference (AIDS 2012) last week in Washington, DC.

Taking a daily aspirin reduces immune activation and activity of platelets -- the cells responsible for blood clotting -- which may help counteract the increased risk of cardiovascular problems among people with HIV taking antiretroviral therapy (ART), researchers reported at the XIX International AIDS Conference (AIDS 2012) last week in Washington, DC.

Several studies have shown that HIV positive people are at increased risk for cardiovascular disease, and a growing body of evidence indicates that inflammation and excessive immune activation contribute to this and other non-AIDS conditions seen at higher rates among people with HIV as they live to older ages.

[More inflammation and immune activation research presented at AIDS 2012]

Meagan O'Brien from New York University Medical School and colleagues conducted a laboratory study of platelet aggregation -- characteristic of clotting or coagulation -- in blood collected from HIV positive people.

Platelet aggregation in vitro has been studied as a biological marker of coronary events and mortality among HIV negative people, they noted. Daily aspirin is often recommended to "thin the blood" and reduce the risk of cardiovascular events such as heart attacks, but it has the potential side effect of gastrointestinal bleeding.

The researchers analyzed platelet aggregation in blood from 25 HIV positive patients on ART for at least 6 months; about half were taking a protease inhibitor and about one-third were on a NNRTI. Most (about 75%) were men, 44% were white, the median age was 50 years, and more than half were smokers. They had undetectable plasma HIV RNA and a high median CD4 T-cell count of about 600 cells/mm3.

This group was compared against 44 healthy HIV negative control subjects, who were not very well matched with regard to cardiovascular risk factors. Just under half were men, 57% were white, the median age was just 27 years, and fewer than 10% were smokers.

The investigators looked at how platelets changed in response to adenosine diphosphate (ADP), which is released when platelets are activated and inhibits further activation; arachidonic acid, a fatty acid involved in cell signaling; collagen, a component of fibrous tissue; epinephrine(aka adrenaline), a hormone with multiple functions including control of the sympathetic nervous system; or no agonist or stimulant (known as spontaneous platelet aggregation).

They then assessed the effects of aspirin -- 81 mg once-daily for 1 week -- on platelet aggregation, activation markers, and various biomarkers of inflammation and coagulation.

Results

  • At baseline, HIV positive people on ART had significantly greater platelet aggregation compared with HIV negative control subjects under 4 of the 5 conditions studied.
  • After taking aspirin for a 1 day, platelet aggregation decreased significantly in the HIV positive group, with the effect being sustained after 1 week.
  • Platelet aggregation in response to arachidonic acid, however, remained significantly higher in the HIV positive group.
  • At baseline, HIV positive participants on ART had a significantly higher percentage of activated (HLA-DR+CD38+) CD4 T-cells and CD8 T-cells.
  • After taking aspirin, the HIV positive participants saw a significant decrease in percentage of activated CD4 cells (from 15% to 11%) and activated CD8 cells (from 14% to 8%).
  • However, no significant changes in activated T-cells were noted among the HIV negative control subjects.
  • Several biomarkers either fell significantly (e.g., activation markers P-selectin and soluble CD14), or showed a downward trend (e.g., inflammation markers high-sensitivity C-reactive protein and interleukin-6, coagulation marker D-dimer).
  • HIV positive participants on ART had more "microparticles," mostly made up of inactivated platelets, than HIV negative controls, even after taking aspirin.

"Platelet activity is increased in HIV-infected subjects on suppressive ART, which may contribute to their heightened cardiovascular risk," the researchers concluded. "One week of 81 mg of aspirin attenuated platelet activation and immune activation in HIV-infected subjects on suppressive ART."

8/10/12

Reference

M O'Brien, MA Nardi, E Montenont, et al. Increased platelet activity and immune activation in HIV-positive subjects on antiretroviral therapy is attenuated with low-dose aspirin. XIX International AIDS Conference (AIDS 2012). Washington, DC, July 22-27, 2012. Abstract THAB0202.