This research study is being performed to find out if Truvada (tenofovir/emtricitabine), an antiviral drug with activity against the Epstein Barr virus (EBV), can reduce EBV levels in saliva and blood in people with multiple sclerosis (MS). A second goal is to find out if Truvada (tenofovir/ emtricitabine) is safe and tolerable in people with MS.

The proposed trial is built on the premise that multiple sclerosis (MS) is, in part, triggered by infection with the human herpesvirus Epstein Barr virus (EBV), and that targeting the virus could be a more effective and safer strategy for MS treatment than immunomodulation or immunosuppression alone. The evidence supporting a causal role for EBV in MS initially came from epidemiological studies that showed similarities in the distribution of infectious mononucleosis and MS, a 2-3 fold increased MS risk among individuals with a clinical history of infectious mononucleosis, and by compelling evidence that MS rarely, if ever, develops in individuals who are not infected with EBV. Furthermore, in a longitudinal study based on the Department of Defense Serum Repository with samples from over 7 million young adults free of MS, individuals who were EBV-seronegative at baseline did not develop symptoms of MS until at least several months after EBV seroconversion, and high serum antibody titers against the EBV-encoded nuclear antigen-1 were associated with an over 30-fold increase in MS risk.

Antiviral agents repurposed from treating other herpesviruses, like acyclovir or valacyclovir, have had minimal clinical efficacy against EBV in studies for infectious mononucleosis and multiple sclerosis. Prodrugs of tenofovir, such as tenofovir disoproxil fumarate (TDF), are significantly more potent inhibitors of EBV replication in cell culture than other drugs that have been clinically ineffective for EBV. TDF is a safe drug used clinically for HIV pre-exposure prophylaxis (PrEP) in HIV-negative patients as the drug Truvada. Truvada has been widely used since its approval in 2004 for the treatment of human immunodeficiency virus (HIV), and has a well-known safety profile that makes it a good candidates for clinical studies.

Inclusion Criteria:

• Provision of signed and dated informed consent form
• Stated willingness and ability to comply with all study procedures and availability for the duration of the study
• Age: 18+
• Established diagnosis of multiple sclerosis
• Evidence of Epstein Barr virus (EBV) infection by serological testing for EBV antibodies antibodies (subjects will have EBV testing performed at the pre-screening visit and if serologies are negative, the subjects will be removed from the study)

Exclusion Criteria:

• Pregnancy or lactation
• Known allergic reactions to components of Truvada
• Previous treatment with Truvada or Descovy
• Unknown HIV status (subjects must have completed HIV antigen/antibody and viral load testing within the prior 6 months to being enrolled or have the testing completed at the pre-screening visit)
• Active or latent hepatitis B (HBV) (subjects must have completed HBV serologies - HbsAg, anti-HBs, and anti-HBc - within the prior 6 months to being enrolled or have the testing completed at the pre-screening visit)
• Current symptoms of severe, progressive, or uncontrolled renal, hematologic, gastrointestinal, pulmonary, cardiac, or neurologic disease, or other medical conditions that, in the opinion of the investigator, might place the subject at unacceptable risk for participation in this study
• Creatinine clearance (CrCl) <75mL/min, as calculated by the Cockcroft-Gault equation
• Urine dipstick for protein and glucose, excluding values of "1 +" or greater
• Any history of bone fractures not explained by trauma
• Confirmed Grade 2 or greater hypophosphatemia
• Any Grade 2 or greater toxicity on screening tests and assessments
• Taking a medication with known interactions with Truvada including but not limited to: Acyclovir, valacyclovir, adefovir, cabozantinib, carbamazepine, cidofovir, cladribine, cobicistat, diclofenac, multiple non-steroidal antiinflammatories (NSAIDs) or chronic high dose NSAIDs, fosphenytoin or phenytoin, ganciclovir, valganciclovir, oxcarbazepine, phenobarbital, primidone, rifabutin, rifampin, rifapentine, sofosbuvir, tipranavir, or other drugs that significantly affect renal function
• Current treatment with drugs known to affect EBV replication as listed below: Acyclovir, valacyclovir, ganciclovir, valganciclovir, famciclovir, teriflunomide, interferon