TAF for HIV-HBV With Renal Dysfunction

Prospective Cohort Study to Assess the Safety and Efficacy of Replacing Tenofovir Disoproxil Fumarate by Tenofovir Alafenamide in HIV/HBV-coinfected Patients With Mild or Moderate Renal Dysfunction

The investigators aim at describing changes in renal glomerular and tubular function with after the switch from TDF to TAF in HIV/HBV-coinfected patients with mild to moderate renal dysfunction and to assess the virological efficacy of TAF on HBV infection.

The study will include HIV/HBV-coinfected participants of the Swiss HIV Cohort Study (SHCS) who are under active care and have been on a stable, TDF-containing ART regimen for at least 6 months. Only patients with an estimated glomerular filtration rate (GFR) between 30 ml/min and 90 ml/min will be included. All individuals who agree to participate will be switched from a TDF-containing ART regimen to a TAF-containing triple ART regimen at week 0 and will be followed for 48 weeks after the treatment change.

Study Overview

• Status: Completed
• Conditions: HIV and Hepatitis B Coinfection
• Intervention / Treatment: Drug: Tenofovir Alafenamide

Detailed Description

Rationale:

Tenofovir alafenamide (TAF) has been shown to cause less renal complications than tenofovir disoproxil fumarate (TDF) while having the same virological efficacy against HIV and HBV infections. In a recent study from the USA and Japan, over 90% of HIV/HBV-coinfected individuals had a suppressed HBV viral load 48 weeks after TDF was replaced by TAF. Thus, TAF might be a valuable treatment option for HIV/HBV-coinfected individuals with TDF-toxicity, especially in the context of resistance to lamivudine and entecavir. However, the safety and efficacy of TAF has not been evaluated to date in HIV/HBV-coinfected patients with renal dysfunction.

Primary objectives:

• To evaluate changes in glomerular and tubular renal function after switch from TDF to TAF in HIV/HBV coinfected patients with renal dysfunction
• To assess the HBV virological efficacy of TAF in HIV/HBV coinfected patients with renal dysfunction switching from TDF to TAF.

Secondary objectives:

• To assess the percentage of and reasons for treatment interruptions
• To describe toxicity events including liver-related complications
• To evaluate changes in liver fibrosis

Intervention:

In eligible patients willing to participate and who have signed an informed consent TDF will be replaced by TAF on day 1 of the study.

Products:

• Tenofovir alafenamide/emtricitabine (TAF/FTC) Dose: one tbl. once per day in addition to at least one third compound OR
• Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (EVG/COBI/FTC/TAF) Dose: one tbl. once per day

Study Population: eligible patients from all 7 centers of the Swiss HIV Cohort Study will be considered.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • Klinik für Infektiologie und Spitalhygiene, Universitätspital Basel
  • Bern, Switzerland, 3010
    • Inselspital
  • Geneva, Switzerland, 1211
    • Department of Infectious Diseases, Hôpitaux Universitaires de Genève
  • Zürich, Switzerland, 8091
    • Klinik für Infektionskrankheiten & Spitalhygiene, Universitätsspital Zürich
  • Saint Gallen
    • St. Gallen, Saint Gallen, Switzerland, 9007
      • Kantonsspital St. Gallen
  • Ticino
    • Lugano, Ticino, Switzerland, 6903
      • Ospedale Regionale di Lugano
  • Vaud
    • Lausanne, Vaud, Switzerland, 1004
      • Cabinet médical Chave-Crottaz-Roggerto
  • Vaude
    • Lausanne, Vaude, Switzerland, 1011
      • Centre Hospitalier Universitaire Vaudois (Chuv)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• HIV/HBV-coinfection
• Suppressed HIV-viremia (<200 cp/ml)
• On TDF-containing ART since at least 6 months
• eGFR > 30 ml/min and <90 ml/min
• Written informed consent

Exclusion Criteria:

• Study drug considered by the treating physician not a valid option for the patient
• Pregnancy
• Decompensated liver cirrhosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Switch; Patients are switched from a TDF-containing antiretroviral therapy regimen to a TAF-containing regimen	Drug: Tenofovir Alafenamide; Patients are switched to either Genvoya (TAF/FTC/EVG/COB) or another FTC/TAF-containing ART regimen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in renal function	Assessment of change in eGFR and tubular markers during the first year of TAF-containing ART	48 weeks
HBV suppression	Evaluation of HBV virological suppression and HBsAg loss after 12 months of TAF	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment interruptions	Description of the proportion of patients with treatment changes or interruptions	48 weeks
Adverse events	Evaluation of the proportion of patients with adverse events during therapy, including grade 2 or above transaminases elevations	48 weeks
Liver fibrosis change	Assessment of the proportion of patients with a change in liver fibrosis stage	48 weeks

Collaborators and Investigators

• Sponsor: University Hospital Inselspital, Berne
• Investigators: Study Chair: Gilles Wandeler, MD MSc, University Hospital Inselspital, Berne

Publications and helpful links

General Publications

• Surial B, Beguelin C, Chave JP, Stockle M, Boillat-Blanco N, Doco-Lecompte T, Bernasconi E, Fehr J, Gunthard HF, Schmid P, Walti LN, Furrer H, Rauch A, Wandeler G; and the Swiss HIV Cohort Study. Brief Report: Switching From TDF to TAF in HIV/HBV-Coinfected Individuals With Renal Dysfunction-A Prospective Cohort Study. J Acquir Immune Defic Syndr. 2020 Oct 1;85(2):227-232. doi: 10.1097/QAI.0000000000002429.

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2017
• Primary Completion (Actual): December 5, 2019
• Study Completion (Actual): December 5, 2019

Study Registration Dates

• First Submitted: April 10, 2017
• First Submitted That Met QC Criteria: April 10, 2017
• First Posted (Actual): April 14, 2017

Study Record Updates

• Last Update Posted (Actual): March 4, 2020
• Last Update Submitted That Met QC Criteria: March 3, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: HIV; Hepatitis B; tenofovir alafenamide; Renal dysfunction
• Additional Relevant MeSH Terms: Digestive System Diseases; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Kidney Diseases; Urologic Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis B; Hepatitis; Renal Insufficiency; Coinfection; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir
• Other Study ID Numbers: INSEL-HINF-2017-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No