Chronic Kidney Diease, Kidney Failure, Pharmacokinetics, Tenofovir, Tenofovir Alafenamide Fumarate
Conditions
Keywords
tenofovir, TAF, chronic kidney disease, kidney failure, pharmacokinetics
Brief summary
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).
Detailed description
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.
Interventions
DIAGNOSTIC_TESTPlasma sampling for tenofovir and emtricitabine
Samples will be used to measure tenofovir and emtricitabine concentrations
DRUGDescovy
Participants will be taking Descovy together with other antiretroviral agents as part of their routine clinical care.
Sponsors
King's College Hospital NHS Trust
Gilead Sciences
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Plasma tenofovir area under the concentration time curve (AUC0-24h) | Days 1 and 2 (24 hours after an observed dose of tenofovir alafenamide) |
| Peak plasma tenofovir concentrations (Cmax) | Day 1 |
| Plasma tenofovir through (Cmin) concentration | Day 2 (24 hours post-dose) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Intracellular tenofovir-diphosphate concentrations | Day 1 | Intracellular TFV-DP (tenofovir diphosphate) concentrations in peripheral blood mononuclear cells (in a subset of participants) and dried blood spots |
| Intracellular emtricitabine-triphosphate concentrations | On Day 1 | Intracellular emtricitabine-triphosphate concentrations in peripheral blood mononuclear cells (in a subset of patients) and dried blood spots (DBS) |
| Plasma tenofovir alafenamide concentrations | Day 1 | — |
| Plasma emtricitabine area under the concentration time curve (AUC0-24h) | Day 1/2 | — |
| Peak plasma emtricitabine concentration (Cmax) | Day 1 | — |
| Plasma emtricitabine through (Cmin) concentration | Day 2 (24h post dose) | — |
Countries
United Kingdom
Contacts
CONTACTFrank A Post, MBChB, MMed(med), PhD
Outcome results
None listed