Antiviral Drugs for Long COVID

Overseen By David Putrino

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Icahn School of Medicine at Mount Sinai

Must not be taking: Antivirals, NSAIDs, Immunosuppressants, others

Disqualifiers: Autoimmune conditions, HIV+, Hepatitis, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 12 weeks

90 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking any medications that interact with Truvada or Selzentry at least 6 weeks before starting the study. If you are currently using Truvada, Selzentry, or medications affecting EBV replication, you cannot participate.

What data supports the effectiveness of the drug Tenofovir disoproxil/emtricitabine (Truvada) for Long COVID?

The drug Tenofovir disoproxil/emtricitabine (Truvada) has shown effectiveness in treating HIV and hepatitis B, as it is a potent antiviral combination. While there is no direct evidence for its use in Long COVID, its antiviral properties in other conditions suggest potential benefits. ^{1 2 3 4 5}

How is the drug Tenofovir disoproxil/emtricitabine unique for treating Long COVID?

Tenofovir disoproxil/emtricitabine is unique for Long COVID as it targets the RNA polymerase of the virus, potentially reducing viral load, and is already known for its effectiveness against HIV and hepatitis B. This drug is taken as a single daily pill, which is convenient compared to other treatments that may require more frequent dosing or different administration routes. ^{4 5 6 7 8}

What is the purpose of this trial?

The trial will test if two repurposed HIV antivirals can reduce symptom burden in adult participants with Long Covid compared to placebo. Viral infection and viral reactivation have been documented in Long Covid. Participants will be randomly allocated to receive antivirals, Truvada (tenofovir disoproxil/emtricitabine, TDF/FTC, Group 1) or Selzentry (Group 2), or a placebo (pill) (Group 3), taken daily for 90 days.

Research Team

David Putrino, PhD, PT

Principal Investigator

Icahn School of Medicine at Mount Sinai

Eligibility Criteria

Adults suffering from Long Covid, who experience ongoing symptoms after recovering from the initial COVID-19 infection. Participants must be willing to take medication daily for 90 days. Specific inclusion and exclusion criteria details are not provided.

Inclusion Criteria

I am willing and able to follow all study rules and attend all appointments.

Provision of signed and dated informed consent form

I had or was suspected to have COVID-19 at least 6 months ago.

Exclusion Criteria

I have been diagnosed with moderate to severe low phosphate levels.

I have had bone fractures without any injury.

I am not taking medications that affect EBV replication.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive either Truvada, Selzentry, or a placebo daily for 90 days

12 weeks

3 visits (in-person) at Day 0, Day 45, and Day 90

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

1 visit (in-person) at Day 180

Treatment Details

Interventions

• Tenofovir disoproxil/emtricitabine

Trial Overview The trial is examining if two HIV antivirals, Truvada (tenofovir disoproxil/emtricitabine) or Selzentry, can alleviate Long Covid symptoms compared to a placebo. Patients will be randomly assigned to one of three groups and treated for 90 days.

Participant Groups

Group I: Truvada (Tenofovir Disoproxil Fumarate, TDF/FTC, tenofovir disoproxil/emtricitabine) Experimental Treatment 1 Intervention

Participants will take 300mg tenofovir disoproxil fumarate/200 mg emtricitabine, once per day, oral capsule for 90 days.

Group II: Selzentry Experimental Treatment 1 Intervention

Participants will take 300 mg of Selzentry, twice a day, oral capsule for 90 days.

Group III: Placebo Placebo Group 1 Intervention

Participants will take a placebo, once per day, oral capsule for 90 days.

Tenofovir disoproxil/emtricitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Truvada for:

• HIV-1 infection
• Pre-exposure prophylaxis (PrEP)

Approved in United States as Truvada for:

• HIV-1 infection
• Pre-exposure prophylaxis (PrEP)
• Post-exposure prophylaxis (PEP)

Approved in Canada as Truvada for:

• HIV-1 infection
• Pre-exposure prophylaxis (PrEP)

Approved in Japan as Truvada for:

• HIV-1 infection

Who Is Running the Clinical Trial?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

PolyBio Research Foundation

Collaborator

Trials

3

Recruited

250+

Yale University

Collaborator

Trials

1,963

Recruited

3,046,000+

PolyBio Research Foundation

Collaborator

Findings from Research

In a study of 59 patients with lamivudine-resistant chronic hepatitis B, switching to tenofovir disoproxil fumarate (TDF) monotherapy significantly improved the rate of complete virological response (CVR) compared to continuing lamivudine plus adefovir, with CVR rates reaching 96.43% at week 48 for the TDF group versus only 29.03% for the LAM plus ADV group.

TDF treatment also led to a higher normalization rate of alanine aminotransferase (75% at week 12) compared to the LAM plus ADV group, indicating better liver function recovery, with no significant adverse effects reported in either treatment group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tenofovir disoproxil fumarate is superior to lamivudine plus adefovir in lamivudine-resistant chronic hepatitis B patients. Yang, DH., Xie, YJ., Zhao, NF., et al.[2022]

In a phase 3 trial with 663 HIV-infected adults, switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) showed similar effectiveness in maintaining viral suppression, with 88.6% of TAF users and 89.1% of TDF users achieving HIV-1 RNA levels below 50 copies per milliliter after 96 weeks.

Patients switching to TAF experienced improvements in kidney function and bone mineral density compared to those remaining on TDF, indicating that TAF may offer a safer profile with better long-term health outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brief Report: Long-Term (96-Week) Efficacy and Safety After Switching From Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in HIV-Infected, Virologically Suppressed Adults. Raffi, F., Orkin, C., Clarke, A., et al.[2022]

In a study involving 81 HIV-infected adolescents treated with tenofovir disoproxil fumarate (TDF) for a median of 96 weeks, TDF was well tolerated with no deaths or discontinuations due to safety concerns.

At week 144, TDF treatment led to significant improvements in bone mineral density and virologic responses, with only 6% of subjects experiencing notable decreases in bone density, indicating that TDF can be a safe and effective option for treating HIV in adolescents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term efficacy and safety of tenofovir disoproxil fumarate in HIV-1-infected adolescents failing antiretroviral therapy: the final results of study GS-US-104-0321. Della Negra, M., De Carvalho, AP., De Aquino, MZ., et al.[2015]

Truvada, a combination of tenofovir disoproxil fumarate and emtricitabine, is effective in treating HIV-1 and HIV-2, allowing for once-daily dosing due to its long half-life and favorable safety profile, including a lower incidence of fat loss compared to other treatments.

The combination has shown superior efficacy in clinical trials compared to other regimens, with a low incidence of resistance mutations, making it a reliable option in highly active antiretroviral therapy (HAART).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tenofovir disoproxil fumarate-emtricitabine coformulation for once-daily dual NRTI backbone. Muñoz de Benito, RM., Arribas López, JR.[2015]

Truvada, a once-daily combination pill containing tenofovir disoproxil fumarate and emtricitabine, is expected to be an effective and low-toxicity treatment option for managing HIV, especially in developing countries.

While there is limited clinical efficacy data available, existing studies suggest that emtricitabine is as potent as lamivudine, and trials have shown that tenofovir combined with lamivudine is effective when paired with other antiretroviral medications for up to 96 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of tenofovir disoproxil fumarate and emtricitabine combination in HIV-infected patients. Gazzard, BG.[2019]

In a study of 50 HIV-infected Koreans receiving Tenofovir disoproxil fumarate (TDF), significant changes in renal function were observed, particularly a decrease in estimated glomerular filtration rate (eGFR) over 144 weeks, indicating potential renal injury from long-term TDF use.

By 144 weeks, 26% of participants experienced a clinically meaningful decline in eGFR, highlighting the importance of monitoring renal function in patients on TDF therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Change in Renal Function among HIV-Infected Koreans Receiving Tenofovir Disoproxil Fumarate-Backbone Antiretroviral Therapy: A 3-Year Follow-Up Study. Lee, KH., Lee, JU., Ku, NS., et al.[2022]

In a pilot study involving 60 outpatients with recent COVID-19, treatment with tenofovir disoproxil fumarate and emtricitabine showed a significant increase in viral clearance by day 7 compared to standard care, suggesting it may help reduce SARS-CoV-2 viral load.

The treatment was generally well-tolerated, although some patients experienced mild gastrointestinal side effects, indicating that while effective, monitoring for adverse effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Tenofovir Disoproxil Fumarate and Emtricitabine on nasopharyngeal SARS-CoV-2 viral load burden amongst outpatients with COVID-19: A pilot, randomized, open-label phase 2 trial. Parienti, JJ., Prazuck, T., Peyro-Saint-Paul, L., et al.[2022]

Tenofovir disoproxil fumarate (TDF) is an effective treatment for both HIV and hepatitis B, highlighting its dual role in managing viral infections.

TDF can be combined with other anti-HIV medications to create effective treatment regimens, such as the once-daily pill Truvada, and can also be used prophylactically to prevent HIV transmission, either orally or as a topical gel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tenofovir: quo vadis anno 2012 (where is it going in the year 2012)? De Clercq, E.[2015]

References

1. United States pubmed.ncbi.nlm.nih.gov

Tenofovir disoproxil fumarate is superior to lamivudine plus adefovir in lamivudine-resistant chronic hepatitis B patients. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Brief Report: Long-Term (96-Week) Efficacy and Safety After Switching From Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in HIV-Infected, Virologically Suppressed Adults. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Long-term efficacy and safety of tenofovir disoproxil fumarate in HIV-1-infected adolescents failing antiretroviral therapy: the final results of study GS-US-104-0321. [2015]

4. England pubmed.ncbi.nlm.nih.gov

Tenofovir disoproxil fumarate-emtricitabine coformulation for once-daily dual NRTI backbone. [2015]

5. England pubmed.ncbi.nlm.nih.gov

Use of tenofovir disoproxil fumarate and emtricitabine combination in HIV-infected patients. [2019]

6. Korea (South) pubmed.ncbi.nlm.nih.gov

Change in Renal Function among HIV-Infected Koreans Receiving Tenofovir Disoproxil Fumarate-Backbone Antiretroviral Therapy: A 3-Year Follow-Up Study. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Effect of Tenofovir Disoproxil Fumarate and Emtricitabine on nasopharyngeal SARS-CoV-2 viral load burden amongst outpatients with COVID-19: A pilot, randomized, open-label phase 2 trial. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Tenofovir: quo vadis anno 2012 (where is it going in the year 2012)? [2015]