 |
|
|
| |
Aspirin Quiets Platelet and Immune Activation in Antiretroviral Responders
|
| |
| |
XIX International AIDS Conference, July 22-27, 2012, Washington, DC
from Jules: this was a small initial study with preliminary findings that although hopeful, surprising & promising need further study in a larger group to confirm, we don't know if the findings if repeated will be clinically significant for patients.
Mark Mascolini
One week of aspirin therapy dampened platelet and immune activation in HIV-positive people with an undetectable viral load and a good CD4 count while taking antiretroviral therapy (ART) [1].
Inflammation-induced platelet aggregation has been proposed as a mechanism explaining higher rates of cardiovascular disease in HIV-positive people than in the general population. Research suggests that platelet aggregation is a strong marker of coronary events and death [2-4].
To pursue this line of study, researchers at New York University (NYU) compared platelet aggregation and immune activation in 25 antiretroviral responders on treatment for more than 6 months (76% of them men) and 44 healthy HIV-negative controls (48% of them men). The HIV-positive people had a median CD4 count of 630, and all had an undetectable viral load.
The NYU team measured platelet aggregation in study participants in response to adenosine diphosphate (ADP, 0.4, 1, and 2 uM for 300 seconds and 10 minutes), arachidonic acid (AA, 150 and 1500 uM for 300 seconds and 10 minutes), collagen (0.05, 0.2, and 1 ug/mL for 300 seconds and 10 minutes), epinephrine (0.1, 0.4 and 2 uM for 300 seconds and 10 minutes), or without agonist (spontaneous platelet aggregation for 300 seconds and 10 minutes). They also measured concentrations of activated CD4 and CD8 cells in HIV-positive people and controls. Then they assessed the impact on these markers of 1 week of aspirin at a dose of 81 mg.
Median age was higher in the HIV group than in controls (50 versus 27), a lower proportion of HIV-positive people was white (44% versus 57%), a higher proportion black (52% versus 2%), and a lower proportion Hispanic (56% versus 93%). The HIV group had a higher proportion of current smokers (56% versus 6%), while family history of myocardial infarction was similar in the two groups (16% and 14%). Half of the HIV group (52%) was taking a protease inhibitor, 36% were taking a nonnucleoside, 16% raltegravir, and 20% abacavir.
Compared with HIV-negative volunteers, people with HIV had higher platelet aggregation in four of the five conditions studied. Aspirin significantly inhibited platelet aggregation in HIV-positive people at 1 day and 1 week. For example, aggregation in response to 150 uM of AA for 10 minutes fell from 54.9% at baseline to 9.1% after 1 day of aspirin (P < 0.0001) and to 9.8% after 1 week (P < 0.001). Despite the aspirin course, however, platelet aggregation in response to AA remained significantly higher in HIV-positive people than in HIV-negative controls.
Compared with HIV-negative controls, the HIV group had significantly higher proportions of activated (HLA-DR+ CD38+) CD4 cells and activated CD8 cells. Proportions of activated T cells fell significantly after 1 week of aspirin therapy--from 14.5% to 10.6% for CD4 cells and from 14.1% to 7.6% for CD8 cells. T-cell activation levels did not decline in HIV-negative controls after 1 week of aspirin.
Levels of two other markers of T-cell activation, P-selectin and soluble CD14, also declined in HIV-positive people after a week of aspirin. Levels of high-sensitivity C-reactive protein and interleukin-6, markers of inflammation, trended downward during a week of aspirin (2.7 to 2.2 mg/L for hsCRP and 203 to 1.98 pg/mL for IL-6), as did levels of the coagulation marker D-dimer (0.23 to 0.13 mcg/mL).
The NYU investigators concluded that "platelet activity is increased in HIV-infected subjects on suppressive ART, which may contribute to their heightened cardiovascular risk."
In 2009 the US Preventive Services Task Force advised physicians to encourage all men from 45 to 79 years old to use prophylactic aspirin "when the potential benefit of a reduction in myocardial infarctions outweighs the potential harm of an increase in gastrointestinal hemorrhage" [5]. Women from 55 to 79 years old should be encouraged to use aspirin "when the potential benefit of a reduction in ischemic strokes outweighs the potential harm of an increase in gastrointestinal hemorrhage."
References
1. O'Brien M, Nardi MA, Montenont E, 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. July 22-27, 2012. Washington, DC. Abstract THAB0202.
2. Malek LA, Spiewak M, Filipiak KJ, et al. Persistent platelet activation is related to very early cardiovascular events in patients with acute coronary syndromes. Kardiol Pol. 2007;65:40-45.
3. Callahan KP, Malinin AI, Atar D, Serebruany VL. Platelet activation as a universal trigger in the pathogenesis of acute coronary events after cocaine abuse. Swiss Med Wkly. 2001;131:487-489.
4. Itoh T, Nakai K, Ono M, Hiramori K. Can the risk for acute cardiac events in acute coronary syndrome be indicated by platelet membrane activation marker P-selectin? Coron Artery Dis. 1995;6:645-650.
5. US preventive Services Task Force. Aspirin for the prevention of cardiovascular disease: US -preventive services task force recommendation statement. Ann Intern Med. 2009;150:396-404.
|
| |
|
|
|
|
|
