Determining the Effect of Abacavir on Platelet Activation

Study Overview
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Brief Summary
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HIV positive patients have a two fold increased risk of developing cardiovascular disease (such as heart attacks and strokes). Cardiovascular disease appears to be due in part to both HIV and the side effects from anti-HIV medications. Abacavir (an important component of current HIV treatment regimens) is one medication shown to be associated with an increase the risk of heart attacks in some studies. The mechanism by which abacavir does this is unknown. We hypothesise that abacavir is leading to heart disease by interacting with platelets, which then form blood clots within the arteries supplying the heart, the subsequent blockage of the artery causing a heart attack. This study aims to determine if abacavir increases the activity (or stickiness) of platelets, and thus provide evidence as to how it may be promoting heart attacks. It will consist of 23 HIV positive men who currently have well controlled HIV. Participants will take abacavir for 15 days in addition to their usual anti-HIV medications. A blood sample to assess platelet activity will be taken at baseline, following the 15 days of therapy (i.e. at the time of maximal abacavir effect) and again after a 28 day washout period (to determine if any effects are reversible).

Official Title
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Determining the Effect of Abacavir on Platelet Activation in Virologically Suppressed HIV Positive Men: an Open Label Interventional Study

Conditions
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HIV, Cardiovascular Disease

Intervention / Treatment
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* Drug: Abacavir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: > 18 years of age Male HIV positive Stable non-abacavir containing anti-retroviral regimen Undetectable HIV Viral load Exclusion Criteria: HLA-B*57*01 allele positivity Previous allergy to abacavir Known cardiovascular disease High Baseline cardiovascular risk (Framingham risk score > 20%) Current or recent antiplatelet therapy Pre-existing platelet or bleeding disorder (i.e. Thrombophilia, Thrombocytopenia, Von willebrands disease, Haemophilia) Significant Chronic liver disease Current Methadone use

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Abacavir<br>Abacavir 600mg (as two 300mg tablets) once daily for 15 days | Drug: Abacavir<br> <br> * Other names: Ziagen;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Phosphorylated Vasodilator Stimulated Phosphoprotein (P-VASP) assay |  | Baseline, day 15 and day 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Platelet aggregation | Measurement of the degree of platelet aggregation in response to collagen related peptide and thrombin receptor-agonist peptide | Baseline, Day 15 and day 48 | 
| Platelet specific collagen receptor glycoprotein VI (GPVI) | Measurement of the expression and shedding of platelet specific collagen receptor GPVI | Baseline, Day 15 and Day 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Platelets, HIV, Cardiovascular disease, Acute myocardial infarction, Abacavir, Antiretrovirals