Epstein-Barr virus causing multiple sclerosis has become irrefutable. Evidence indicating that EBV not only causes, but drives disease progression is growing. If EBV is a driver of MS then elimination of EBV would be a rational therapy for MS. There are licensed drugs with activity against EBV, such as the antiviral medication tenofovir alafenamide, which may be particularly effective as an inhibitor of EBV lytic reactivation.
See the following dropbox link, or files page, for a number of scientific papers indicating that EBV is the cause and driver of MS disease activity, and on potential antiviral therapies.
Multiple sclerosis is caused by EBV. The risk of MS increased 32-fold after infection with EBV. Serum levels of neurofilament light chain increased only after EBV infection. These findings suggest EBV as the leading cause of MS.
Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis
EBV as a driver of MS.
Epstein-Barr virus as a driver of multiple sclerosis
EBV as the “gluten of MS” hypothesis provides a rationale for trialing antiviral therapies
The case for targeting latent and lytic Epstein-Barr virus infection in multiple sclerosis
Epstein-Barr virus as a cause of multiple sclerosis: opportunities for prevention and therapy
Latent, Lytic, and Linked to Multiple Sclerosis—How EBV Drives Autoimmunity
Targeting EBV is a viable therapeutic target in MS
EBV-specific T-cell responses are telling us something important about multiple sclerosis
Discoveries beyond molecular mimicry describe how EBV drives multiple sclerosis
Dysregulated Epstein-Barr virus infection in the multiple sclerosis brain
EBV Early Lytic Antigens, EBNA2 and PDL-1, in Progressive Multiple Sclerosis Brain
Intrathecal CD8 T-cells of multiple sclerosis patients recognize lytic Epstein-Barr virus proteins
Broader Epstein–Barr virus–specific T cell receptor repertoire in patients with multiple sclerosis
Unstable EBV latency drives inflammation in multiple sclerosis patient derived spontaneous B cells
EBV infection and HLA-DR15 jointly drive multiple sclerosis by myelin peptide presentation
EBV dysregulation is associated with immune imbalance in multiple sclerosis
There is a reduced risk of developing MS in HIV positive patients taking antiretroviral therapy (ART). There are also several cases of patients who presented indefinite remission or resolution of MS symptoms after induction of ART.
Human immunodeficiency virus and multiple sclerosis: a review of the literature
Risk of Multiple Sclerosis in People Living with HIV: An International Cohort Study
Case Reports
In the era of antiviral trials for MS, the answer lies in the details
Radiologic and clinical stability in an HIV-negative MS patient after tenofovir: An updated case report
Could antiretrovirals be treating EBV in MS? A case report
Tenofovir as a treatment option for multiple sclerosis
Antiviral therapy with tenofovir in MS
HIV infection and multiple sclerosis: a case with unexpected “no evidence of disease activity” status
Long-term MRI and clinical stability in an HIV-positive patient with multiple sclerosis on tenofovir: A case report
The patients in the above case reports are taking tenofovir prodrugs, tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide fumarate (TAF). TAF may be particularly effective as an inhibitor of EBV lytic reactivation, and clinical studies are warranted.
Tenofovir prodrugs potently inhibit Epstein–Barr virus lytic DNA replication by targeting the viral DNA polymerase
The below chart has implications regarding TAF and TDF dose. Fig 5G indicates that the standard dose of TAF would reach a concentration needed to block ∼40% of DNA replication (EC40) mediated by the EBV polymerase after 40 min in their in vitro assay. This indicates that the standard dose of TAF may be lower than optimal for EBV, as the EC90 is a typical therapeutic target. This data comes from an in vitro assay and the optimal dose needs to be determined in humans. Even if the standard dose is lower than optimal for EBV, there are case reports of patients who presented indefinite remission or resolution of MS symptoms taking a standard dose of TAF or TDF.
Descovy is a fixed-dose combination antiretroviral medication of tenofovir alafenamide 25mg / emtricitabine 200mg, commonly prescribed by PrEP clinics for HIV pre-exposure prophylaxis.
Descovy
Tenofovir alafenamide fumarate (TAF) and tenofovir disoproxil fumarate (TDF), are both tenofovir prodrugs that improve the absorption and delivery of tenofovir, which gets converted into its active form (TFV-DP) inside cells to stop viral replication. TAF is a newer generation prodrug designed for better tissue targeting, allowing for lower doses. A 25mg dose of TAF leads to higher tenofovir concentrations in lymphocytes compared to a 300mg dose of TDF. TDF at 300mg daily has been used for PrEP for over a decade. This may indicate that doses of TAF greater than 25mg are safe long term, however this needs further study.
The authors of this paper created a list of therapies with anti-EBV effects.
Below are clinical trials looking at tenofovir and other antiviral agents for treatment of MS.
Effects of Antiviral Therapies on Epstein-Barr Virus Replication
Fatigue In Relapsing Multiple Sclerosis – Epstein Barr Virus (FIRMS-EBV) Treatment Trial