Tenofovir Abacavir Platelet Activation Study

Study Overview
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Brief Summary
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Some but not all observational studies have found that current exposure to abacavir is associated with increased risk of cardiovascular events such as myocardial infarction, stroke and cardiovascular death. This study aim to investigate possible adverse effect of abacavir on platelet reactivity, coagulation and endothelial activation in HIV-1 infected patients. The study is an open-labeled cross-over trial, where patients receiving antiretroviral therapy containing abacavir switch treatment to a regimen containing tenofovir and vice versa for a period of 90 days.

Official Title
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Changes in Coagulation and Platelet Reactivity in HIV-1 Infected Patients Switching Between Abacavir and Tenofovir Containing Antiretroviral Regimens

Conditions
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HIV

Intervention / Treatment
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* Drug: abacavir (600 mg QD)
* Drug: tenofovir (245 mg QD)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-1 infected Can understand and sign written informed consent Received one of the above mentioned antiretroviral regimens continuously ≥ 6 months HIV RNA < 400 copies/mL for ≥ 6 months Exclusion Criteria: Receiving anticoagulant therapy, adenosine diphosphate (ADP) receptor inhibitors, aspirin or nonsteroidal antiinflammatory drugs (NSAIDs) Previous ischemic heart disease, peripheral atherosclerotic disease or stroke Coagulation disorder (e.g. hemophilia, factor V Leiden mutation) Platelet count < 150 x 109/L during the past 6 months from inclusion Estimated glomerular filtration rate (eGFR) <70 during the past 6 months from inclusion Humane leukocyte antigen (HLA)-B*57:01 positive genotype Hepatitis B or C positive during the past year from inclusion Hypersensitivity to the active substances or to any of the excipients

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 70 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: Other
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tenofovir to abacavir<br>Patients switching from tenofovir (245 mg QD) to abacavir (600 mg QD) | Drug: abacavir (600 mg QD)<br> <br> |
| Experimental: Abacavir to tenofovir<br>Patients switching from abacavir (600 mg QD) to tenofovir (245 mg QD) | Drug: tenofovir (245 mg QD)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in platelet aggregation (Multiplate) before and after switching between abacavir and tenofovir. |  | before and after 90 days intervention | 
| Differences in clot formation kinetics (thromboelastography) before and after switching between abacavir and tenofovir. |  | before and after 90 days intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of plasma lipids |  | Before and after 90 days intervention | 
| activated partial thromboplastin time (APTT) |  | 90 days | 
| international normalized ratio (INR)/Factor II, VII, X |  | Before and after 90 days intervention | 
| Platelet count |  | Before and after 90 days intervention | 
| Fibrinogen |  | Before and after 90 days intervention | 
| D-dimer |  | Before and after 90 days intervention | 
| Antithrombine |  | Before and after 90 days intervention | 
| Interleukin 6 (IL-6) |  | Before and after 90 days intervention | 
| High sensitivity C reactive protein (HS-CRP) |  | Before and after 90 days intervention | 
| Soluble P-Selectin |  | Before and after 90 days intervention | 
| soluble CD40 ligand (sCD40L) |  | Before and after 90 days intervention | 
| Syndecan-1 |  | Before and after 90 days intervention | 
| Soluble E-selectin |  | Before and after 90 days intervention | 
| Tissue plasminogen activator |  | Before and after 90 days intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV-1, Abacavir, Platelet activation, Thromboelastography, Coagulation