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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether two antiviral drugs, typically used for HIV, can reduce symptoms in people with Long Covid. Participants will be randomly assigned to take either Truvada (tenofovir disoproxil/emtricitabine), Selzentry, or a placebo pill daily for 90 days. The goal is to determine if these drugs can lessen the symptom burden, including headaches, memory loss, and fatigue, that many Long Covid sufferers experience. Individuals who have had Long Covid symptoms for at least six months after a confirmed or suspected COVID-19 infection may be eligible to participate. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that both Selzentry and Truvada are generally well-tolerated. Selzentry, or maraviroc, has been studied for conditions like Long COVID. These studies indicate it is usually safe, but monitoring for possible side effects, such as liver problems, is important.

Truvada, which contains tenofovir disoproxil and emtricitabine, also has a good safety record. People using these drugs for conditions like HIV generally tolerate them well. Common side effects include mild nausea or headache, while serious issues are rare.

Both treatments have received FDA approval for other uses, suggesting their safety. However, discussing potential risks with a healthcare provider remains important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for Long COVID because they introduce antiviral drugs, Tenofovir disoproxil and Emtricitabine, which are typically used for HIV but may help fight lingering viral infections in Long COVID patients. Unlike the standard care options that often focus on symptom management, such as pain relievers or physical therapy, these drugs target the virus directly. Another investigational treatment in the trial, Selzentry, also known as Maraviroc, is being explored for its potential to block specific pathways the virus might use to persist in the body. This approach could offer a new way to tackle the root cause of Long COVID symptoms rather than just alleviating them.

What evidence suggests that this trial's treatments could be effective for Long COVID?

Studies have shown that the drug combination tenofovir disoproxil/emtricitabine may reduce the risk of severe COVID-19. People taking these drugs were less likely to need hospital or ICU care. Research also suggests it could help prevent the virus from spreading in the body. In this trial, some participants will receive tenofovir disoproxil/emtricitabine. Promising results have emerged for Selzentry (also known as maraviroc) in treating Long COVID symptoms. Some patients reported improvement when using maraviroc as part of their treatment. Selzentry is another treatment option under study in this trial. Both treatments are being examined for their potential to ease ongoing Long COVID symptoms. ^{1 3 4 6 7}

Who Is on the Research Team?

David Putrino, PhD, PT

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

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

Provision of signed and dated informed consent form

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

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.

Known allergic reactions to components of Truvada or Selzentry

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Truvada (Tenofovir Disoproxil Fumarate, TDF/FTC, tenofovir disoproxil/emtricitabine) Experimental Treatment 2 Interventions

Participants will take 300mg tenofovir disoproxil fumarate/200 mg emtricitabine, once per day, and one placebo capsule 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, twice 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

Published Research Related to This Trial

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]

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]

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]

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]

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 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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S1684118225001422

Maraviroc treatment for hospitalized participants with non- ... More than 200 symptoms associated with long-COVID have shown to have a negative impact on multiple organ system.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06974084

NCT06974084 | Investigating Measurable PRO Acuity Trial ... The IMPACT Long Covid Treatment clinical study (IMPACT-LC) is testing two repurposed and previously approved drugs, Maraviroc and Atorvastatin, for the ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9944830/

Case series: Maraviroc and pravastatin as a therapeutic ... Post-acute sequelae of COVID (PASC), or long COVID, is a multisystem complication of SARS-CoV-2 infection that continues to debilitate ...

4. firstwordpharma.com firstwordpharma.com/story/5934576

HealthBio Therapeutics Begins FDA-Approved Fast-Track ... Since 2020, his team has focused on Long COVID and PASC, treating more than 12,000 patients with a protocol of maraviroc and atorvastatin to ...

5. medrxiv.org medrxiv.org/content/10.1101/2024.11.27.24317656v1.full-text

Patient-Reported Treatment Outcomes in ME/CFS and ... This study underscores the symptomatic and therapeutic similarities between ME/CFS and Long COVID and highlights the commonalities and nuanced complexities of ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06974084

NCT06974084 | Investigating Measurable PRO Acuity Trial ... The IMPACT Long Covid Treatment clinical study (IMPACT-LC) is testing two repurposed and previously approved drugs, Maraviroc and Atorvastatin, for the ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11493926/

Post-acute sequelae of SARS-CoV-2 infection (Long COVID ... Long COVID, also known as PASC (post-acute sequelae of SARS-CoV-2), is a complex infection-associated chronic condition affecting tens of millions of people ...