Pharmacokinetics of JULUCA in Hemodialysis

Inclusion Criteria

• Negative HIV antibody testing at screening.
• For the ESRD requiring HD study group: ESRD requiring chronic hemodialysis for at least 6 months at an established center (not home dialysis).

NOTE: The approximate date that hemodialysis was initiated should be reported, if known.

For the normal renal function group: Estimated CrCl (using the Cockcroft-Gault equation) at screening ≥75mL/min.

• Availability of alternative venous access (not used for dialysis) for the purpose of PK sampling.
• The following laboratory values obtained within 30 days prior to study entry (obtained either at screening or done as part of routine clinical care):
• AST (SGOT) and ALT (SGPT) less than or equal to ULN
• Total bilirubin less than or equal to 1.5 x ULN
• Hemoglobin greater than or equal to 8.0 mg/dL
• A negative serum pregnancy test result at screening for all women of reproductive potential who have not reached menopause or undergone hysterectomy, bilateral oophorectomy, or tubal ligation.
• Males and females, age 18-65 years.
• Ability and willingness of participant or legal guardian/representative to provide written informed consent.

Exclusion Criteria

• Known allergy or hypersensitivity to either dolutegravir or rilpivirine
• Use of peritoneal dialysis.
• Serious illnesses, other than ESRD, requiring systemic treatment and/or hospitalization within 30 days prior to the Screening Visit.
• 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).
• Hepatitis B surface antigen or hepatitis C antibody with detectable RNA at screening.
• Known gastrointestinal disease that may lead to poor absorption of the study drugs.
• Known hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption.
• 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
• 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.
• Use of proton pump inhibitors within 7 days of initiating study drug (H2 blockers are permitted).
• Pregnancy and/or breast-feeding.
• Moderate to severe depression, defined as a PHQ-9 ≥ 10 at Screening.
• 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.
• QTc interval greater than 500 msec at Screening.