Effects of Ledipasvir/Sofosbuvir on the Pharmacokinetics and Renal Safety of Tenofovir Alafenamide (TAF)

University of Colorado Denver (CU Denver)

Status and phase: Completed; Phase 4

Conditions: HIV Coinfection; Hepatitis C

Treatments: Drug: TDF with a boosted protease inhibitor; Drug: TAF with a boosted protease inhibitor; Drug: TAF with a boosted protease inhibitor and LDV/SOF

Study type: Interventional

Funder types: Other

Identifiers

NCT03126370

17-0490

Details and patient eligibility

About

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.

Enrollment: 10 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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

Trial design

Primary purpose: Other

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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10 participants in 1 patient group

TAF with a boosted PI and LDV/SOF

Experimental group

Description:

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.

Treatment:

Drug: TAF with a boosted protease inhibitor and LDV/SOF

Drug: TAF with a boosted protease inhibitor

Drug: TDF with a boosted protease inhibitor