Increased platelet activity and immune activation in HIV-positive subjects on antiretroviral therapy is attenuated with low-dose aspirin
Background: Mechanisms for increased
cardiovascular risk in HIV-infected adults are incompletely understood, but heighted
inflammation leading to a pro-thrombotic state has been proposed as a major
contributor. In vitro platelet aggregation
has been studied as a robust biological marker of coronary events and mortality.
Methods: We studied platelet
aggregation in 25 HIV-infected subjects on ART with undetectable plasma HIV-1
RNA, median CD4 537 cells/mm3 (73.9%men) and 29 healthy HIV seronegative controls
(44.4%men) in response to submaximal adenosine diphosphate (ADP, 0.4uM) , arachidonic
acid (AA, 0.15mM), or without agonist (spontaneous
platelet aggregation [SPA]). The effects of one week of aspirin 81mg
daily on activation markers, as measured by flow cytometry, and platelet aggregation
were investigated. Two-tailed paired t tests and non-parametric Mann-Whitney U test
tests were used for statistical analyses, with results given as medians with interquatile
to controls, HIV subjects on ART had increased platelet aggregation in response
to ADP (10.8% [6.5, 42.3] vs 7.6% [3.3, 10.2], p=0.02), AA (54.9% [8.7, 89.9]
vs 11% [2.5, 77.6], p< 0.05), and without agonist (SPA) 7.5% [4.7, 11.4] vs
5% [2.9, 9.1], p< 0.05). Following aspirin therapy, percent aggregation in
response to ADP and AA decreased significantly (p< 0.01 for each comparison).
Compared to controls, HIV subjects on ART had increased %HLADR+CD38+ CD4+ Tcells(8.3%[4.1,
12.1] vs 3.9%[1.4, 6.1], p=0.01) and %HLADR+CD38+ CD8+ Tcells (0.46%[0.21,
0.58] vs 0.21%[0.18, 0.34], p=0.01). Following
aspirin therapy there was a significant decrease in % HLADR+CD38+ CD4+ Tcells,
p< 0.01 and a trend in decreased % HLADR+CD38+ CD8+ Tcells, p=0.08, in HIV
subjects but no significant change was noted in controls.
Conclusions: Platelet activity is
increased in HIV-infected subjects on suppressive ART, which may contribute to
their heightened cardiovascular risk. One week of 81mg of aspirin attenuated
platelet activation and immune activation in HIV-infected subjects on
19th International AIDS Conference
"M.O'Brien, et al.
Increased platelet activity and immune activation in HIV-positive subjects on antiretroviral therapy is attenuated with low-dose aspirin.
19th International AIDS Conference: