TAF for HIV-HBV With Renal Dysfunction

HIV and Hepatitis B Coinfection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03115736
• Other study ID #: INSEL-HINF-2017-1
• Status: Completed
• Phase: Phase 2
• Start date: May 23, 2017
• Est. completion date: December 5, 2019

Study information

• Verified date: March 2020
• Source: University Hospital Inselspital, Berne
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: December 5, 2019
• Est. primary completion date: December 5, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Coinfection
• Hepatitis
• Hepatitis B
• HIV and Hepatitis B Coinfection
• Renal Insufficiency

Intervention

Drug:
• Tenofovir Alafenamide
Patients are switched to either Genvoya (TAF/FTC/EVG/COB) or another FTC/TAF-containing ART regimen

Locations

Country	Name	City	State
Switzerland	Klinik für Infektiologie und Spitalhygiene, Universitätspital Basel	Basel
Switzerland	Inselspital	Bern
Switzerland	Department of Infectious Diseases, Hôpitaux Universitaires de Genève	Geneva
Switzerland	Cabinet médical Chave-Crottaz-Roggerto	Lausanne	Vaud
Switzerland	Centre hospitalier universitaire vaudois (CHUV)	Lausanne	Vaude
Switzerland	Ospedale Regionale di Lugano	Lugano	Ticino
Switzerland	Kantonsspital St. Gallen	St. Gallen	Saint Gallen
Switzerland	Klinik für Infektionskrankheiten & Spitalhygiene, Universitätsspital Zürich	Zürich

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Inselspital, Berne

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in renal function	Assessment of change in eGFR and tubular markers during the first year of TAF-containing ART	48 weeks
Primary	HBV suppression	Evaluation of HBV virological suppression and HBsAg loss after 12 months of TAF	48 weeks
Secondary	Treatment interruptions	Description of the proportion of patients with treatment changes or interruptions	48 weeks
Secondary	Adverse events	Evaluation of the proportion of patients with adverse events during therapy, including grade 2 or above transaminases elevations	48 weeks
Secondary	Liver fibrosis change	Assessment of the proportion of patients with a change in liver fibrosis stage	48 weeks