The TAF-DELTA Study: Dose Escalation of Tenofovir Alafenamide on Epstein–Barr Virus Activity in Healthy Individuals
The TAF-DELTA study is an early-phase clinical trial investigating whether tenofovir alafenamide (TAF), a well-established antiviral medication, can safely reduce Epstein–Barr virus (EBV) activity in healthy adults carrying the virus. Growing evidence suggests that EBV plays a key role in the development of multiple sclerosis (MS), highlighting the need for effective antiviral strategies. By examining the safety, tolerability, and biological effects of increasing doses of TAF, this study aims to generate important knowledge that may support the development of future treatments targeting EBV-related diseases, including MS.
Disease: Epstein–Barr virus infection (EBV)
Type of study: Interventional trial
Coordinating Investigator: Andrea Kyvik Habbestad
Study Director: Øivind Torkildsen
Background: Novel insights from our MS Node and others indicate that Epstein–Barr virus (EBV) infection is a necessary cause of multiple sclerosis (MS). EBV infection is lifelong, and periodic viral reactivation may contribute to immune activation and disease progression. However, there are currently no approved antiviral therapies targeting EBV.
Tenofovir alafenamide fumarate (TAF) is a nucleotide analogue with established safety in HIV and hepatitis B treatment. Recent in vitro studies have demonstrated that TAF potently inhibits lytic EBV replication, with markedly stronger effects than conventional antiherpesvirus drugs. Clinical data on the effect of TAF on EBV activity in humans are lacking, and the optimal dose required to achieve antiviral effects against EBV is unknown.
The TAF-DELTA study is designed as a first-in-human dose-escalation study to evaluate the safety and biological effects of increasing doses of TAF on EBV activity in healthy EBV-seropositive individuals. The study will generate critical safety and mechanistic data to inform the design of future randomised controlled trials targeting EBV in MS and other EBV-associated diseases.
Objective: The primary objective of the study is to evaluate the safety and tolerability of escalating doses of tenofovir alafenamide fumarate (25 mg, 50 mg, and 100 mg daily) in healthy EBV-seropositive individuals.
Secondary objectives are to investigate the effect of TAF on EBV oral shedding in saliva, EBV-specific CD4⁺ T-cell responses measured by ELISPOT, and EBVspecific IgG antibody levels.
Design: This is a prospective, phase IIa, interventional, within-participant dose-escalation study, as a part of the EBV-MS Horizon Europe project. A total of 45 healthy EBV-seropositive adults aged 18–65 years will be included. Participants will undergo a four-week baseline period without treatment, followed by sequential treatment with TAF 25 mg daily for four weeks, 50 mg daily for four weeks, and 100 mg daily for four weeks, with close safety monitoring throughout the study.
The primary endpoint is the number of participants experiencing treatment-emergent adverse events or serious adverse events during the study period.
Secondary endpoints include changes in EBV shedding frequency in saliva, EBV-specific CD4⁺ T-cell responses, and EBV-specific antibody levels at each dose level compared with baseline.
Status: Regulatory approvals are currently being obtained. First patient inclusion is planned for spring 2026. Recruitment is expected to be completed within six months, and final study completion is anticipated in early 2027.
Participating centres:
• Haukeland University Hospital, Bergen, Norway
• Oslo University Hospital, Oslo, Norway
Funding:
• The Regional Health Authority of Western Norway
• Haukeland University Hospital
• The University of Bergen