Pharmacokinetics of JULUCA in Hemodialysis

Exclusion Criteria

• •1. Known allergy or hypersensitivity to either dolutegravir or rilpivirine
• •2. Use of peritoneal dialysis.
• •3. Serious illnesses, other than ESRD, requiring systemic treatment and/or hospitalization within 30 days prior to the Screening Visit.
• •4. Known liver cirrhosis, unstable liver disease (presence of ascites, encephalopathy, coagulopathy, esophageal/gastric varices), Child-Pugh Class A, B, or C, or known biliary abnormalities (except for known Gilbert's syndrome or asymptomatic gallstones).
• •5. Hepatitis B surface antigen or hepatitis C antibody with detectable RNA at screening.
• •6. Known gastrointestinal disease that may lead to poor absorption of the study drugs.
• •7. Known hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption.
• •8. Any of the following gastrointestinal signs or symptoms of Grade ≥ 2 within 7 days prior to the Screening Visit or during study drug administration prior to the Intensive PK Study Visit:
• •* nausea
• •* vomiting
• •* diarrhea
• •* abdominal pain
• •9. Use of any of the following within 30 days of initiating study drug:
• •* Medications known to appreciably inhibit or induce CYP3A enzymes, P-glycoprotein, or UGT1A1 or UGT1A4 enzymes (e.g., anticonvulsants such as carbamazepine, phenytoin, oxacarbamazepine; antimycobacterials such as rifampin, rifabutin and rifapentine; antifungal agents such as ketoconazole, fluconazole and itraconazole; verapamil, clarithromycin, erythromycin)
• •* St. John's Wort, echinacea, grapefruits or grapefruit juice, garlic supplements, ginseng, golden seal, and milk thistle
• •* Cancer chemotherapeutic agents
• •* Investigational agents
• •* Immunomodulators, including systemic steroids greater than or equal to 100 mg/day of prednisone (Note: Topical and inhaled corticosteroids are allowed.)
• •* Dofetilide
• •* Positive pre-study drug screen. Drugs that will be screened for include amphetamines, barbiturates, cocaine and phencyclidine (PCP). Active injected drug users will be excluded from this study.
• •10. Use of proton pump inhibitors within 7 days of initiating study drug (H2 blockers are permitted).
• •11. Pregnancy and/or breast-feeding.
• •12. Moderate to severe depression, defined as a PHQ-9 ≥ 10 at Screening.
• •13. Significant change (i.e., more than a 50% change) in tobacco smoking habit within 6 weeks prior to the Screening Visit. Participants who have recently stopped smoking should have stopped smoking more than 6 weeks prior to the Screening Visit. Participants who have recently started smoking should have started more than 6 weeks prior to the Screening Visit.
• •14. QTc interval greater than 500 msec at Screening.