Effects of Ledipasvir/Sofosbuvir on the Pharmacokinetics and Renal Safety of Tenofovir Alafenamide (TAF)
- Conditions
- Hepatitis CHIV Coinfection
- Interventions
- Drug: TDF with a boosted protease inhibitorDrug: TAF with a boosted protease inhibitorDrug: TAF with a boosted protease inhibitor and LDV/SOF
- Registration Number
- NCT03126370
- Lead Sponsor
- University of Colorado, Denver
- Brief Summary
This study will evaluate the effect of ledipasvir/sofosbuvir (LDV/SOF) treatment on the pharmacokinetics (PK) and renal safety of tenofovir in the form of tenofovir alafenamide (TAF). Subjects living with human immunodeficiency virus (HIV) who are receiving tenofovir-based antiretroviral therapy (in the form of tenofovir disoproxil fumarate \[TDF\]), and are also taking a ritonavir- or cobicistat-boosted protease inhibitor will be invited to participate.
The study will consist of five visits: a screening visit, three abbreviated 4-hour pharmacokinetic visits, and one end-of-study follow-up visit.
Subjects will also be asked to use a Wisepill device, which will track medication adherence throughout the study.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 10
- Between 18-70 years of age
- Have been taking TDF and a ritonavir- or cobicistat-boosted protease inhibitor as part of standard care for treatment of HIV
- eGFR < 30 mL/min
- Pregnant or planning pregnancy
- Breastfeeding
- Any medical, social, or mental-health issue(s) that, in the opinion of the investigators, could interfere with study participation or the study outcomes
- Signs or symptoms of decompensated liver disease
- Hepatitis B infection
- Medications that may cause unwanted drug interactions with ledipasvir/sofosbuvir or emtricitabine/tenofovir alafenamide
- Unwillingness or inability to comply with study procedures
- Chronic hepatitis C infection
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description TAF with a boosted PI and LDV/SOF TDF with a boosted protease inhibitor Participants who are already taking tenofovir disoproxil fumarate 300 mg (in the form of Viread or Truvada) in combination with either a ritonavir- or cobicistat-boosted protease inhibitor for HIV treatment will continue to take their prescribed treatment for 12 weeks after enrollment. Participants will be switched from tenofovir disoproxil fumarate to tenofovir alafenamide (TAF) 25 mg/emtricitabine (FTC) 200 mg (Descovy) with a boosted protease inhibitor for the next 12 weeks. After taking TAF/FTC for 12 weeks, participants will then start taking ledipasvir 90mg/sofosbuvir 400mg (LDV/SOV, Harvoni) in combination with TAF/FTC and a boosted protease inhibitor for 4 weeks. Participants will then return to taking TAF/FTC with a boosted protease inhibitor for the final 12 weeks of the study. TAF with a boosted PI and LDV/SOF TAF with a boosted protease inhibitor Participants who are already taking tenofovir disoproxil fumarate 300 mg (in the form of Viread or Truvada) in combination with either a ritonavir- or cobicistat-boosted protease inhibitor for HIV treatment will continue to take their prescribed treatment for 12 weeks after enrollment. Participants will be switched from tenofovir disoproxil fumarate to tenofovir alafenamide (TAF) 25 mg/emtricitabine (FTC) 200 mg (Descovy) with a boosted protease inhibitor for the next 12 weeks. After taking TAF/FTC for 12 weeks, participants will then start taking ledipasvir 90mg/sofosbuvir 400mg (LDV/SOV, Harvoni) in combination with TAF/FTC and a boosted protease inhibitor for 4 weeks. Participants will then return to taking TAF/FTC with a boosted protease inhibitor for the final 12 weeks of the study. TAF with a boosted PI and LDV/SOF TAF with a boosted protease inhibitor and LDV/SOF Participants who are already taking tenofovir disoproxil fumarate 300 mg (in the form of Viread or Truvada) in combination with either a ritonavir- or cobicistat-boosted protease inhibitor for HIV treatment will continue to take their prescribed treatment for 12 weeks after enrollment. Participants will be switched from tenofovir disoproxil fumarate to tenofovir alafenamide (TAF) 25 mg/emtricitabine (FTC) 200 mg (Descovy) with a boosted protease inhibitor for the next 12 weeks. After taking TAF/FTC for 12 weeks, participants will then start taking ledipasvir 90mg/sofosbuvir 400mg (LDV/SOV, Harvoni) in combination with TAF/FTC and a boosted protease inhibitor for 4 weeks. Participants will then return to taking TAF/FTC with a boosted protease inhibitor for the final 12 weeks of the study.
- Primary Outcome Measures
Name Time Method Change From Week 12 Plasma Tenofovir Area Under the Plasma Concentration vs. Time Curve From Time 0 to 24 Hours (AUC0-24) at 24 and 28 Weeks 12 weeks and 24 weeks and 28 weeks Compare plasma tenofovir AUC0-24 between TAF with boosted PI vs. TDF with boosted PI (Phase 2 vs. 1), and between TAF with boosted PI and LDV/SOF vs. TDF with boosted PI (Phase 3 vs. 1)
Change From Week 12 Tenofovir-diphosphate (TFV-DP) in Peripheral Blood Mononuclear Cells (PBMCs) at 24 and 28 Weeks 12 weeks, and 24 weeks and 28 weeks Compare tenofovir-diphosphate (TFV-DP) in peripheral blood mononuclear cells (PBMCs) between TAF with a boosted PI vs. TDF with a boosted PI (Phase 2 vs. 1), and TAF with a boosted PI and LDV/SOF vs. TDF with a boosted PI (Phase 3 vs. 1).
- Secondary Outcome Measures
Name Time Method Change From Week 12 Tenofovir-diphosphate (TFV-DP) in Dried Blood Spots (DBS) 12 weeks and 24 and 28 weeks Compare tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) between TAF with a boosted PI vs. TDF with a boosted PI (Phase 2 vs. 1), and TAF with a boosted PI and LDV/SOF vs. TDF with a boosted PI (Phase 3 vs. 1)
Change in Estimated Glomerular Filtration Rate (eGFR) and Renal Biomarkers: eGFR 12 weeks, 24 weeks, and 28 weeks Change in estimated glomerular filtration rate (eGFR)
Change in Estimated Glomerular Filtration Rate (eGFR) and Renal Biomarkers: UPCR 12 weeks, 24 weeks, and 28 weeks Change in estimated glomerular filtration rate (eGFR) and renal biomarkers: Urine protein to creatinine ratio (UPCR)
Change in Estimated Glomerular Filtration Rate (eGFR) and Renal Biomarkers: B2M/Cr Ratio, and RBP/Cr Ratio 12 weeks, 24 weeks, and 28 weeks Change in renal biomarkers: urinary beta-2 microglobulin (B2M)/creatinine (Cr) ratio, and urinary retinol binding protein (RBP)/Cr ratio
Trial Locations
- Locations (1)
University of Colorado Hospital
🇺🇸Aurora, Colorado, United States