Rationale for Antiretroviral Therapy for MS
See the following dropbox for a number of scientific papers that have informed my understanding that EBV is the cause and driver of MS disease activity, and on potential antiretroviral therapies.
https://www.dropbox.com/scl/fo/1qutcgmeqam2ooly55zk6/AI8REKe5iiNBSkTLl9wxg-k?rlkey=16bed6tj959qdzy3tpfzl2cdg&st=b8l2k7ww&dl=0
I include some information from these papers below. If you want additional information, in a non journal format, regarding MS and EBV please read the MS researcher and neurologist Gavin Giovannoni’s blog. https://gavingiovannoni.substack.com/
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.
https://www.science.org/doi/10.1126/science.abj8222
EBV may cause MS through the below mechanisms. If EBV is a driver of MS then elimination of EBV would be a rational therapy for MS.
https://www.science.org/stoken/author-tokens/ST-413/full
https://www.msard-journal.com/article/S2211-0348(22)00516-8/fulltext
https://www.nature.com/articles/s41586-022-04432-7
https://www.nature.com/articles/s41467-025-61751-9
https://rupress.org/jem/article/219/11/e20220650/213431/Broader-Epstein-Barr-virus-specific-T-cell
https://pmc.ncbi.nlm.nih.gov/articles/PMC9915775/pdf/nihpp-rs2398872v1.pdf
Looking at antiretroviral therapies (ART) to treat EBV, there is a reduced risk of developing MS in HIV positive patients taking ART. There are also several cases of patients who presented indefinite remission or resolution of MS symptoms after induction of antiretroviral therapy.
https://neurolrespract.biomedcentral.com/articles/10.1186/s42466-019-0030-4
Case Studies
https://pubmed.ncbi.nlm.nih.gov/29510325/
https://www.sciencedirect.com/science/article/abs/pii/S221103482030643X
https://journals.sagepub.com/doi/full/10.1177/0300060521999577
https://www.sciencedirect.com/science/article/abs/pii/S2211034823008969
The patients in the above case studies are taking tenofovir prodrugs. Tenofovir may be particularly effective as an inhibitor of EBV lytic reactivation, and clinical studies are warranted.
https://www.pnas.org/doi/10.1073/pnas.2002392117
The below chart is very important. Fig 5G indicates that the standard dose of Tenofovir Alafenamide (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 is lower than you would like for EBV, as the EC90 is a typical therapeutic target.
https://www.pnas.org/cms/10.1073/pnas.2002392117/asset/239315fc-4c3d-480f-9ae5-7335a57b5b4d/assets/graphic/pnas.2002392117fig05.jpeg
Descovy is a fixed-dose combination antiretroviral medication of Tenofovir Alafenamide / Emtricitabine, used for HIV PrEP and HBV infection, and is considered very safe.
https://www.descovy.com/side-effects
Tenofovir Disoproxil Fumarate (TDF) and Tenofovir Alafenamide Fumarate (TAF), 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.
You get a higher Tenofovir concentration in your lymphocytes taking a 25mg dose of TAF vs a 300mg dose of TDF. People have been taking 300mg doses daily of TDF for PrEP for over a decade now. This makes me optimistic that up to 300mg of TAF would be safe.
https://www.descovyhcp.com/taf-pharmacology
This paper created a good list of therapies with anti-EBV effects from existing reviews. They assessed these candidates for potential usefulness and possible harm in MS.
https://pubmed.ncbi.nlm.nih.gov/39792343/
Below are some ongoing clinical trials looking at TAF for MS.
https://mstrials.org.au/fatigue-in-relapsing-multiple-sclerosis-epstein-barr-virus-firms-ebv-treatment-trial/
https://www.helse-bergen.no/en/neuro-sysmed-english/clinical-studies-at-neuro-sysmed/ms--clinical-studies/taf-ms-2/
A clinical trial for Tenofovir Alafenamide as an add-on to anti-CD20 therapies is cancelled due to lack of funding. Patients on B cell depleters could follow their design.
https://clinicaltrials.gov/ct2/show/NCT04880577
