Effects of Ledipasvir/Sofosbuvir on the Pharmacokinetics and Renal Safety of Tenofovir Alafenamide (TAF)
Condition: Hepatitis C; HIV Coinfection
MeSH terms: Hepatitis C; Coinfection; HIV Infections
Intervention: TDF with a boosted protease inhibitor; TAF with a boosted protease inhibitor; TAF with a boosted protease inhibitor and LDV/SOF
Intervention 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.
Other: Blood draws for tenofovir PK, renal function assessment; Participants will be switched from tenofovir disoproxil fumarate to tenofovir alafenamide 25 mg/emtricitabine 200 mg with a boosted protease inhibitor.
Other: Blood draws for tenofovir PK, renal function assessment; After taking tenofovir alafenamide/emtricitabine for 12 weeks, participants will then start taking ledipasvir 90 mg/sofosbuvir 400 mg (Harvoni) in combination with the tenofovir alafenamide 25 mg/emtricitabine 200 mg (Descovy) and a boosted protease inhibitor for 4 weeks. Subjects will then return to taking tenofovir alafenamide 25 mg/emtricitabine 200 mg (Descovy) and a boosted protease inhibitor for the final 12 weeks.
Other: Blood draws for tenofovir PK, renal function assessment
Intervention MeSH terms: Emtricitabine tenofovir alafenamide; Emtricitabine; Tenofovir; HIV Protease Inhibitors; Protease Inhibitors
Phase: Phase 4
Study type: Interventional
Primary purpose: Other
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        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