Study to determine the effect of steady-state plasma concentration of Tipranavir/ritonavir (TPV/r) on platelet aggregation in healthy subjects and investigate the effect of TPV/r at steady state plasma concentrations on other platelet functions and biomarkers of coagulation and fibrinolysis.

Inclusion Criteria:

1. Ability and willingness to give written informed consent to participate in this study (i.e., prior to any study-specific procedures)

2. Age ≥18 years and ≤50 years

3. Female subjects of child-bearing potential were eligible if:

   • They had used a barrier contraceptive method for at least 12 weeks before administration of study medication and had a negative serum pregnancy test result during the screening period (Day - 35 to Day -3); or,
   • Were abstinent for more than 12 weeks before screening and had a negative serum pregnancy test result during the screening period (Day -35 to Day -3); or,
   • Had a documented tubal ligation and had a negative serum pregnancy test result during the screening period (Day -35 to Day -3)

4. Ability to swallow capsules without difficulty

5. Reasonable probability of completing the study

6. Findings from medical history, physical examination and 12-lead ECG indicating subject was healthy and suitable for the trial in the opinion of the investigator

7. Agreement to abstain from alcohol consumption or drugs of abuse during the study

8. Agreement to abstain from ingestion of grapefruit, grapefruit juice, Seville oranges, or orange marmalade from screening period to the end of the study

9. Negative urine drug screen for drugs of abuse

10. Non smoker

11. Agreement to abstain from use of tobacco products from screening period to the end of the study

12. Negative HIV-1 serology by ELISA testing

13. Negative Hepatitis B surface Antigen test (HBsAg)

14. Negative Hepatitis C Virus antibody (anti-HCV) test by Enzyme Immunoassay

15. Platelet count ≥125,000/mm3

16. Hemoglobin ≥11.0 g/dL

17. Prothrombin time ≤1.0 x upper limit of normal (ULN)

18. Activated Partial thromboplastin time ≤1.0 x ULN

Exclusion Criteria:

1. Female subjects who:

   • had a positive serum pregnancy test during the screening period (Day -35 to Day -3) or during the study
   • were breast feeding or planing to breast feed at any time from the screening period through 30 days after the last dose of the study drug
   • were not willing to use a barrier method of contraception at any time from screening period through 30 days after the last dose of the study drug
   • were taking any hormonal therapy for any reason such as birth control or replacement therapy

2. Had used any investigational agent within 30 days prior to Visit 2

3. Blood or plasma donations (>100 mL total) for research or altruistic reasons within 30 days prior to Visit 2

4. Had used aspirin or any non-steroidal anti-inflammatory agent (NSAID), and including COX-2 inhibitors, dipyridamole, clopidogrel, ticlopidine or other antiplatelet drugs within 14 days prior to Visit 2 or during the study

5. Active peptic ulceration or history of peptic ulcer disease

6. Known history of or suspected hypersensitivity to aspirin, any NSAID or any other component of the test drugs (Tipranavir, Darunavir, Ritonavir)

7. Known hypersensitivity to antiretroviral drugs (marketed or experimental drug in clinical research studies)

8. Active bleeding disorder or history of active bleeding disorder

9. Active Intra cranial hemorrhage (ICH) or history of ICH

10. Active coronary artery disease or history of coronary artery disease

11. Alcohol abuse (more than 60 g/day)

12. Any indication for current use of aspirin or any NSAID or indication for such use from Visit 2 to Visit 18

13. Had used any over-the-counter medication within 7 days prior to Visit 2, or current use of any prescription drug

14. Subjects who had an abnormal laboratory result of Grade 1 or greater, as defined by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS), (result must have been available at least 3 days prior to Visit 2-Day 1), except the following screening laboratory values:

    • serum potassium, serum sodium, serum phosphate and uric acid, where central laboratory reference ranges will be used to determine eligibility rather than DAIDS table; or,
    • amylase or creatinine results of Grade 1 on DAIDS table if these results are considered clinically not significant by investigator; or
    • other marginally abnormal laboratory values not considered clinically significant by investigator and approved by clinical monitor

15. History of any illness that in the opinion of the investigator might confound the results of the study or pose additional risks in administering aspirin, Tipranavir, Darunavir, or Ritonavir

16. Hypersensitivity to sulphonamide drugs

17. Had used proton pump inhibitors during 14 days prior to Visit 2

18. Vitamin E intake in excess of 60 mg/day within 30 days prior to Visit 2

19. Vitamin E supplementation in excess of 60 mg/day during the study (Vitamin E content of multivitamin tablets is allowed)