Clinical trial NCT03115736: TAF for HIV-HBV With Renal Dysfunction
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV and Hepatitis B Coinfection
Keywords: HIV
Hepatitis B
Renal dysfunction
tenofovir alafenamide
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
First posted: 2017-04-14
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in renal function
timeFrame: 48 weeks
measure: HBV suppression
timeFrame: 48 weeks
Secondary outcomes:
measure: Treatment interruptions
timeFrame: 48 weeks
measure: Adverse events
timeFrame: 48 weeks
measure: Liver fibrosis change
timeFrame: 48 weeks
Other outcomes:
Locations:
city: St. Gallen
country: Switzerland
facility: Kantonsspital St. Gallen
state: Saint Gallen
city: Lugano
country: Switzerland
facility: Ospedale Regionale di Lugano
state: Ticino
city: Lausanne
country: Switzerland
facility: Centre hospitalier universitaire vaudois (CHUV)
state: Vaude
city: Lausanne
country: Switzerland
facility: Cabinet médical Chave-Crottaz-Roggerto
state: Vaud
city: Basel
country: Switzerland
facility: Klinik für Infektiologie und Spitalhygiene, Universitätspital Basel
city: Bern
country: Switzerland
facility: Inselspital
city: Geneva
country: Switzerland
facility: Department of Infectious Diseases, Hôpitaux Universitaires de Genève
city: Zürich
country: Switzerland
facility: Klinik für Infektionskrankheiten & Spitalhygiene, Universitätsspital Zürich
Study officials:
affiliation: Insel Gruppe AG, University Hospital Bern
name: Gilles Wandeler, MD MSc
role: STUDY_CHAIR
References:
citation: 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.