Tales of the Medically Unexpected: Could the HIV drug Tenofovir arrest multiple sclerosis?

A collective sense of relief and elation may be a common reaction to big breakthroughs in medical research. But accidentally finding that a drug which has been sitting on a pharmacy shelf for years might unexpectedly treat an unrelated, debilitating condition can spark a profound sense of wonder. All the more so when the unrelated condition is both devastating and has few treatment options.

A gathering chorus of case reports suggests a potentially transformative link between antiviral therapies—developed to treat HIV infection—and the management of multiple sclerosis (MS). While MS is an autoimmune disorder, a growing body of evidence convincingly implicates Epstein-Barr virus (EBV) as a driver of MS pathogenesis.  Based on a growing number of striking case studies, questions are being asked about whether repurposing HIV medications could offer a new frontier in MS treatment.

The Catalyst: Remarkable Individual Recoveries

The momentum for this research was sparked by extraordinary individual case studies. One of the most famous reports, featured by the BBC, followed a woman in Sussex who had become dependent on a wheelchair to get around, due to the progressive of her MS [1]. After fearing she may have been exposed to HIV her doctor prescribed a regimen of antiretroviral drugs. Within days she experienced an unexpected and dramatic recovery, rapidly regaining the ability to walk and climb stairs.

This individual case is not isolated. A more recent case study, published in Multiple Sclerosis and Related Disorders, detailed an HIV-positive patient with MS who exhibited "no evidence of disease activity" while taking the antiretroviral therapy tenofovir, developed for treatment of HIV [2]. For years, the patient remained clinically and radiologically stable, with MRI scans showing no new lesions. Other case reports further support this, documenting similar radiologic and clinical stabilisation of MS following use of tenofovir [3]. These "accidental" successes have forced researchers to ask why drugs designed to block the replication of a retrovirus (HIV) may have the potential to stop or reverse the progression of an autoimmune disease like MS.

The Biological Link: EBV and Tenofovir

The leading hypothesis focuses on EBV. Recent studies have established EBV infection as a leading cause of MS [4]. While tenofovir was developed to treat HIV infection, it has also been found to potently inhibit the replication and reactivation of EBV (5). Tenofovir was originally developed as the pro-drug tenofovir disoproxil fumarate (TDF), however renal side effects led to the development of a safer alternative pro-drug, tenofovir alafenamide (TAF). While both are active against EBV, TAF has slightly greater anti-EBV activity than TDF.

When EBV reactivates in the body, it may drive immune responses that damage myelin sheaths in MS patients. Antibodies against the EBV lytic antigen EBNA1 may play an important role in this process by cross reacting with proteins on neurons such as GlialCAM  and potentially triggering demyelination [6]. By suppressing EBV viral activity, antivirals like tenofovir may inadvertently shut down a key driver of the MS disease process.

The Path Forward

Large-scale clinical trials are underway to investigate these promising signals. Researchers at Massachusetts General Hospital have started a clinical trial to determine if Truvada (a combination of tenofovir and emtricitabine) can reduce EBV levels in saliva and blood in 50 people with multiple sclerosis [7]. In addition, a randomised double-blind, placebo-controlled trial is underway in Norway and Finland to compare the anti-EBV efficacy and safety of TAF with placebo in people who have relapsing remitting MS [8].

The summary of these reports paints a hopeful picture: if MS is indeed driven by EBV, then the "accidental" recoveries of HIV-positive MS patients may have provided the roadmap for the next generation of MS therapies. Could MS disease activity be shut down by repurposing safe, well characterised and licensed antivirals in a more targeted and less immunosuppressive way? The results of current clinical trials will hopefully tell us.

Handling the unexpected

Findings that challenge an established scientific narrative can present a particular publication challenge when trendy hypotheses dominate the discourse and unprepared minds stifle the editorial boards of key publishers. The data may be sound, but the story still needs to be constructed carefully: the evidence needs to be distinguished from interpretation, alternative explanations addressed and the right journal audience identified. These are precisely the sorts of challenges that experienced medical writers encounter when developing manuscripts from complex or unexpected datasets.

At Niche Science & Technology, this is one of the areas in which our Medical Communications team provides practical support, from manuscript development and journal selection through submission and response to peer review.

References

1. Multiple sclerosis patient walks after taking HIV drugs. BBC News. Oct 2015. https://www.bbc.co.uk/news/uk-england-sussex-34659771
2. Torkildsen O et al. Antiviral therapy with tenofovir in MS. Multiple Sclerosis and Related Disorders. March 2024. DOI: 1016/j.msard.2024.105436
3. Drosu NC, et al. Radiologic and clinical stability in an HIV-negative MS patient after tenofovir: An updated case report. Multiple Sclerosis and Related Disorders. March 2024. DOI: 1016/j.msard.2023.105396
4. Bjornevik K et al. Epstein–Barr virus as a leading cause of multiple sclerosis: mechanisms and implications. Nat Rev Neurol. Feb 2023. DOI: 1038/s41582-023-00775-5
5. Drosu NC, et al. Tenofovir prodrugs potently inhibit Epstein-Barr virus lytic DNA replication by targeting the viral DNA polymerase. Proc Natl Acad Sci USA. June 2020. DOI: 1073/pnas.2002392117
6. Sattarnezhad N et al. Antibody reactivity against EBNA1 and GlialCAM differentiates multiple sclerosis patients from healthy controls. Proc Natl Acad Sci U S A. Mar 2025. DOI: 1073/pnas.2424986122
7. Clinical trial, ‘Effects of Antiviral Therapies on Epstein-Barr Virus Replication’. https://clinicaltrials.gov/study/NCT05957913
8. Clinical trial, ‘TAF-MS 1 study: Tenofovir alafenamide fumarate (TAF) and Epstein-Barr virus activity in people with multiple sclerosis’. https://www.helse-bergen.no/en/neuro-sysmed-english/clinical-studies-at-neuro-sysmed/ms--clinical-studies/taf-ms-1/