Tenofovir Exposures in Advanced Kidney Disease Study

Tenofovir Exposures in People With HIV Who Have Advanced Chronic Kidney Disease and Are Receiving Tenofovir Alafenamide-containing Antiretroviral Therapy

Phamacokinetic study to evaluate tenofovir, emtricitabine and tenofovir alafenamide exposures in people with HIV who have chronic kidney disease stage 4 (estimated glomerular filtration rate [eGFR] 15-29 mL/min/1.73m2) or stage 3 b (eGFR 30-44 mL/min/1.73m).

Participants with chronic kidney disease who are currently being treated with standard doses of tenofovir alafenamide/emtricitabine (25/200 mg as part of unboosted antiretroviral regimens; 10/200 mg on standard as part of boosted antiretroviral regimens) with suppressed HIV RNA will undergo repeated blood sampling over 24 hours to evaluate tenofovir, emtricitabine, tenofovir di-phosphate and emtricitabine tri-phosphate exposures.

Inclusion Criteria:

• Capable of giving informed consent
• Male or female aged 18 years or older
• A history of chronic kidney disease (eGFR <45 for at least 3 months) currently not requiring haemodialysis or peritoneal dialysis
• Current eGFR <30 based on serum creatinine measurement and calculated with the CKD-EPI (2021) formula [6]
• Up to 20 individuals with eGFR 30-44 will be included; such participants require prior CI approval to ensure at least 30 participants with eGFR <30 can be enrolled
• Stable ART regimen (consistent use for at least 3 months)
• ART regimens must contain TAF (administered at standard dose [25mg once daily as part of unboosted regimens; 10 mg once daily as part of ritonavir- or cobicistat-boosted regimens]) and FTC, with any additional retrovirals allowed
• Agreeable to accommodate morning TAF/FTC dosing schedule for one week prior to undergoing the pharmacokinetic assessments
• Well controlled HIV for >6 months
• All available HIV RNA measurements <200 copies/mL
• Stable clinical condition

Exclusion Criteria:

• Dialysis at screening, Day 1, or in the past 90 days prior to Day 1
• ART switch in the past 3 months
• Individuals on ART regimens not containing TAF/FTC, or non-standard doses of TAF/FTC are excluded
• Uncontrolled HIV (HIV RNA >200 copies/mL) or active hepatitis C (HCV RNA positive) in the past 6 months
• Hb <80 g/L or eGFR >45 or HIV RNA >200 copies/mL at screening
• Medications that induce TAF or FTC metabolism, e.g. rifamycins, phenytoin, St Johns Wort
• Current or recent use of entecavir (past 30 days)
• Current or recent (past 30 days) acute clinical complications (e.g. hospitalizations, severe infections or acute graft rejection)
• Pregnancy or lactation (female participants only)