Antivirals in MS: Tenofovir

[frodo]

Long-term MRI and clinical stability in an HIV-positive patient with multiple sclerosis on tenofovir: a case report

https://www.sciencedirect.com/science/a ... 4823008969

Introduction

The Epstein-Barr virus (EBV) is the likely leading cause of multiple sclerosis (MS). (Bjornevik et al., 2022) Debates continue regarding the potential benefit of antiviral treatment for EBV after the onset of MS.

Tenofovir prodrugs, used in highly active antiretroviral therapy (HAART) for HIV treatment, have shown potent inhibition of EBV in B-cells in vitro. (Drosu et al., 2020) Intriguingly, several case reports describe people with MS on HAART containing tenofovir with no evidence of MS disease activity, (Chalkley and Berger, 2014, Delgado et al., 2014, Labella et al., 2021, Francesco and Myriam, 2015, Torkildsen et al., 2020, Skarlis et al., 2018) and epidemiological studies have reported a lower incidence of MS in patients with HIV. (Gold et al., 2015, Nexø et al., 2013)

Although these observations could be due to immunosuppression from HIV, patients on HAART often maintain undetectable viral loads and normal CD4 T cell counts.

This raises the question of whether HIV treatment may be reducing MS disease activity by inadvertently treating EBV. Here, we present the case of an MS patient with significant brain and spinal cord disease burden at diagnosis who has remained clinically and radiologically stable for more than nine years while on a HAART regimen containing tenofovir and in the extended absence of disease-modifying therapies (DMTs) for MS.

Discussion

Although speculative, it is intriguing to consider the possibility that the improvement in this patient's MS condition after her HIV diagnosis was a direct effect of HAART on MS. Interestingly, she was maintained on a regimen containing tenofovir prodrugs for the entirety of her HIV treatment course. While the possibility that the HIV infection itself affected her MS disease course by modulating immune responses cannot be ruled out, she experienced amelioration of incoordination, cognition, and ...

Conclusion

Further research into tenofovir-based therapies for MS is warranted. In the future, it is crucial that trial designs incorporate a rational selection of primary endpoints, drawing from cases such as this one which suggest early treatment with evaluation of MRI disease activity and clinical relapses as suitable endpoints. Rigorous, placebo-controlled trials of antivirals used as monotherapy are essential to answer critical questions concerning the role of EBV in MS.

[frodo]

Radiologic and clinical stability in an HIV-negative MS patient after tenofovir: an updated case report

https://www.sciencedirect.com/science/a ... 4823008957

Introduction

In 2018, members of our team published an interesting case of a patient with newly diagnosed aggressive relapsing-remitting multiple sclerosis (RRMS) who experienced significant improvement in both neurological symptoms and fatigue after starting Combivir (zidovudine/lamivudine) in the absence of disease-modifying therapies (DMTs).

Since this patient was negative for HIV, it prompted an intriguing hypothesis that the effect of treatment may be attributable to the known direct activity of zidovudine as an antiviral against EBV and, therefore, the larger question of whether MS could ultimately be treatable with drugs targeting EBV lytic reactivation.

Given prior negative trials with acyclovir, 2 we suggested that it might be prudent to avoid classical anti-herpesvirus drugs and instead use compounds that bypass the rate-limiting step of viral kinase-dependent drug metabolism, like those used for the treatment of HIV.

Since circumstantial epidemiological evidence of a lower incidence of MS in patients with HIV supported the possible existence of other HIV drugs with anti-EBV effects, our team then screened these compounds for activity against EBV in vitro, which led to the identification of tenofovir prodrugs as compounds with superior anti-EBV activity.

Here, we provide an update on that case and discuss implications for future clinical trials.

[frodo]

In the Era of Antiviral Trials for MS, the Answer Lies in the Details

https://www.msard-journal.com/article/S ... 3/fulltext

Abstract

After a seminal epidemiological study linked infection with the Epstein-Barr virus (EBV) to multiple sclerosis (MS), there is a consensus that EBV is the primary cause of MS ( Bjornevik et al., 2022).

Now, the question remains: How does EBV lead to MS, given that the majority of infected individuals do not develop the disease? Hypotheses addressing this question can be divided into two groups: (1) EBV acts as a trigger of self-perpetuating autoimmunity, or (2) EBV acts as a driver of MS pathology ( Sollid, 2022).

• If EBV is solely a trigger, vaccination strategies to prevent EBV infection may lower the incidence of MS; however, these interventions would not be helpful after an MS diagnosis.

• On the other hand, if EBV is a driver of MS, then targeting EBV using antiviral therapies could reduce disease activity in patients with established MS.

In this issue, we present three compelling case reports of MS patients treated with prodrugs of Tenofovir, a nucleotide analogue that inhibits the EBV DNA polymerase ( Drosu et al., 2020).

These cases have important clinical implications, as they provide insights on whether EBV may act as a driver in MS and how EBV can be targeted in future trials.

[vesta]

Greetings:

According to Dr Zivadinov, a history of Mononucleosis is one of 4 primary factors typical of MS patients. Yes, EBV causes Mono, but it causes other diseases as well. How does Mono in particular "cause" MS? I would suggest that illness damages the vascular system leading to CCSVI, that suppressing EBV after the illness is of little use. One is too fixed on the auto-immune theory, insufficiently aware of the vascular issue.
Regards, Vesta

[DIM]

Case Study Reports Positive Impact of Antiviral Therapy Tenofovir in MS, Warranting Further Research

https://www.neurologylive.com/view/case ... cbvXcCJ_hA