Effect of Aspirin on Abacavir-induced Platelet Reactivity in HIV-infected Patients

Effect of Aspirin on Abacavir-induced Platelet Reactivity in HIV-infected Patients

The specific research questions addressed in the present study are:

• to investigate the impact of treatment with low-dose aspirin in HIV-1-infected patients treated with ABC and test it would result in decreased in vivo platelet activation and platelet hyperreactivity
• to investigate if aspirin has the same effects in HIV-infected as in HIV-uninfected patients.

Highly active antiretroviral therapy (HAART) may reduce the deleterious effects of HIV on the cardiovascular system by decreasing viral load and chronic inflammation; however some antiretrovirals enhance cardiovascular risk due to direct adverse effects on platelets or the endothelium.

Abacavir/lamivudine (ABC/3TC) and tenofovir/emtricitabine (TDF/FTC) are the most widely used nucleoside reverse transcriptase inhibitor (NRTI) associations in HAART. ABC has been initially considered as one of the most benign antiretroviral drugs due to a better metabolic profile than other nucleoside analogues, but since the D.A.D. study reported an association between the use of ABC and an increase in cardiovascular risk there has been controversy around this drug.

Clinical evidence suggests that in vivo platelet activation and platelet hyperreactivity contribute to adverse cardiovascular events and hyperreactive platelets may transform a normal reparative response to a mild arterial injury into an unwanted thrombotic event.

Aspirin is the cornerstone in the prevention of atherothrombotic events, as it has been shown to be effective both in the primary and secondary prevention of MI (6), and its beneficial effects likely involve the modulation of inflammatory and immune pathways. But despite heightened awareness regarding elevated CVD risk among HIV-infected patients, aspirin or others antiplatelet therapy were markedly underprescribed among HIV-infected patients at risk for CVD events (7).

Based on this, the proposed study will assess whether low-dose aspirin, in well-characterized HIV-1-infected patients treated with ABC, would result in decreased in vivo platelet activation and platelet hyperreactivity. Moreover will be investigate if aspirin will have the same effects in HIV-infected as in HIV-uninfected patients.

Inclusion Criteria:

• a viral load <50 copies per millilitre
• ABC treatment for at least 6 months

Exclusion Criteria:

• age younger than 18
• nonsteroidal anti-inflammatory drug use in the past week (including aspirin), renal failure (creatinine clearance <30 mL/min), platelet count <100,000/microL, history of gastrointestinal bleeding within the last 6 months, presence of coexisting inflammatory disease, cancer, active bacterial or fungal infection, bleeding history, oral anticoagulant therapy and allergy to aspirin