Study to determine the effects of combined tipranavir and ritonavir treatment (at steady-state) on the single-dose pharmacokinetics of atorvastatin, the effects of single-dose atorvastatin on the steady-state pharmacokinetics of tipranavir, and the effects of antacid on the pharmacokinetics of tipranavir

Inclusion Criteria:

1. Male and female subjects between 18 and 60 years of age inclusive

2. A Body Mass Index (BMI) between 18 and 29 kg/m2

3. Signed informed consent prior to trial participation

4. Ability to swallow numerous study medications

5. Acceptable laboratory values that indicate adequate baseline organ function are required at the time of screening. Laboratory values are considered to be acceptable if severity is less than or equal to Grade 1, based on the AIDS Clinical Trials Group Grading Scale

6. Acceptable medical history, physical examination and ECG, and chest X-ray (if not conducted within the last 12 months) are required prior to entering the treatment phase of the study

7. Willingness to abstain from alcohol starting 2 days prior to any administration study drug up to the end of the study. Red wine must not be ingested within 5 days prior to treatment and throughout the study

8. Willingness to abstain from the following starting 10 days prior to any administration of study drug up until the end of the study:

   • Grapefruit or grapefruit juice or products containing grapefruit juice

9. Willingness to abstain from ingesting Seville oranges, garlic supplements, St. John's Wort, or Milk Thistle, within 5 days of treatment and for the duration of the study

10. Willingness to abstain from methylxanthine-containing drinks or foods (coffee, tea, cola, energy drinks, chocolate, etc.) within 72 hours of each pharmacokinetic (PK) sampling day and until after the last sample from each of the intensive sampling days is collected

11. Willingness to abstain from over the counter herbal medications for the duration of the study

12. Willingness to abstain from vigorous physical exercise during PK Days

13. Reasonable probability for completion of the study

Exclusion Criteria:

1. Female subjects who are of reproductive potential who:

   • Have positive serum β-human chorionic gonadotropin at Visit 1, or on Day 0
   • Have not been using a barrier contraceptive method for at least 3 months prior to Day 0 (Visit 2)
   • Are not willing to use a reliable method of barrier contraception (such as diaphragm or condoms), during the trial and 30 days after completion/termination
   • Are breast-feeding

2. Use of any pharmacological contraceptive (including oral, patch or injectable contraceptives) for 1 month prior to study initiation and for the duration of the study

3. Use of hormone replacement therapy for 1 month prior to study initiation and for the duration of the study

4. Participation in another trial with an investigational medicine within 60 days prior to Day 0 (Visit 2)

5. Use of any medication listed in the protocol within 30 days prior to Day 0 (Visit 2)

6. Administration of antibiotics within 10 days prior to Day 0 (Visit 2) or during the trial

7. History of acute illness within the past sixty (60) days. Subjects will be excluded for these disorders greater than sixty days if, in the opinion of the investigator, the subject does not qualify as a healthy volunteer

8. Have serological evidence of Hepatitis B or C Virus

9. Have serological evidence of exposure to HIV

10. Recent history of alcohol or substance abuse (within 6 months of study period)

11. Smokers who smoke greater than 10 cigarettes or 3 cigars or 3 pipes per day; inability to refrain from smoking during the trial

12. Blood or plasma donations within 30 days prior to Day 0 (Visit 2) or during the trial

13. Subjects with a seated systolic blood pressure either <100 mm Hg or >150 mm Hg; resting heart rate either <50 beats/min or >90 beats/min

14. Subjects with a history of any illness or allergy that, in the opinion of the investigator,might confound the results of the study or pose additional risk in administering Tipranavir,Ritonavir, atorvastatin or erythromycin to the subject

15. Subjects who are currently taking any over-the-counter drug within 7 days prior to Day 0,(Visit 2) or who are currently taking any prescription drug that, in the opinion of the investigator in consultation with the clinical monitor, might interfere with either the absorption, distribution or metabolism of the test substances

16. Known hypersensitivity to Tipranavir,Ritonavir, sulfonamides, atorvastatin, erythromycin or saccharin

17. Inability to comply with the protocol