Post by Nadica (She/Her) on Jul 5, 2024 23:09:04 GMT
A CLINICAL TRIAL OF REPURPOSED HIV ANTIVIRALS IN LONGCOVID - Last Updated Feb 25, 2024
Project Summary:
A clinical trial to test if two repurposed HIV antivirals (Truvada and Maraviroc) can reduce symptom burden in patients with LongCOVID. Truvada, Maraviroc, or a placebo will be given to participants randomized to one of three groups to take for 90 days. Blood and saliva will be collected from participants at four timepoints and analyzed for infectious, immune, and metabolic biomarkers that may change due to antiviral treatment. This positions the trial as an experimental medicine study capable of uncovering LongCOVID disease mechanisms associated with virus-targeting treatment.
Project background:
A plausible mechanism for Long COVID is persistence of the SARS-CoV-2 virus in tissue and/or the reactivation of latent pathogens. For example, SARS-CoV-2 reservoirs have been identified in LongCOVID gut tissue months after initial infection, and members of the current clinical trial team have documented signs of Epstein Barr Virus reactivation in LongCOVID patients. The activity of Human Endogenous Retroviruses may also increase in some individuals with LongCOVID, potentially contributing to symptoms. It follows that extended treatment with repurposed antiviral medications potentially capable of targeting these viruses may help mitigate Long COVID symptoms.
Truvada is a safe drug used in the treatment of HIV. It has been widely used in this capacity since 2004 and has a well-known safety profile that makes it a good candidate for repurposed clinical trials. Truvada has been shown to have action against SARS-CoV-2 in a lab setting, and is also a potent inhibitor of Epstein Barr Virus replication in cell culture. Marovirac is a chemokine receptor antagonist drug designed to act against HIV by interfering with the interaction between the virus and the human receptor CCR5. The drug may have an impact on viral activity in LongCOVID monocyte immune cells, which express both CCR5 play a role in vascular homeostasis and endothelial immune surveillance. A case series reported significant clinical improvement in LongCOVID patients treated with Marovirac.
Blood and saliva will be collected from each trial participant to best understand mechanisms by which Truvada or Marovirac may provide benefit. Analyses include:
Measurement of SARS-CoV-2 antibody responses, RNA, and proteins (spike, N etc).
Measurement of salivary Epstein Barr Virus load, as well as plasma quantification of antibody responses to EBV antigens.
Measurement of Human Endogenous Retrovirus (HERV) elements including bulk RNA sequencing to determine ERB expression levels from whole blood.
Deep immune profiling, including measurement of cytokines and vascular measures.
Measurement of hormones levels.
Measurement and “score” of vascular and endothelial health via EndoPAT.
Project Summary:
A clinical trial to test if two repurposed HIV antivirals (Truvada and Maraviroc) can reduce symptom burden in patients with LongCOVID. Truvada, Maraviroc, or a placebo will be given to participants randomized to one of three groups to take for 90 days. Blood and saliva will be collected from participants at four timepoints and analyzed for infectious, immune, and metabolic biomarkers that may change due to antiviral treatment. This positions the trial as an experimental medicine study capable of uncovering LongCOVID disease mechanisms associated with virus-targeting treatment.
Project background:
A plausible mechanism for Long COVID is persistence of the SARS-CoV-2 virus in tissue and/or the reactivation of latent pathogens. For example, SARS-CoV-2 reservoirs have been identified in LongCOVID gut tissue months after initial infection, and members of the current clinical trial team have documented signs of Epstein Barr Virus reactivation in LongCOVID patients. The activity of Human Endogenous Retroviruses may also increase in some individuals with LongCOVID, potentially contributing to symptoms. It follows that extended treatment with repurposed antiviral medications potentially capable of targeting these viruses may help mitigate Long COVID symptoms.
Truvada is a safe drug used in the treatment of HIV. It has been widely used in this capacity since 2004 and has a well-known safety profile that makes it a good candidate for repurposed clinical trials. Truvada has been shown to have action against SARS-CoV-2 in a lab setting, and is also a potent inhibitor of Epstein Barr Virus replication in cell culture. Marovirac is a chemokine receptor antagonist drug designed to act against HIV by interfering with the interaction between the virus and the human receptor CCR5. The drug may have an impact on viral activity in LongCOVID monocyte immune cells, which express both CCR5 play a role in vascular homeostasis and endothelial immune surveillance. A case series reported significant clinical improvement in LongCOVID patients treated with Marovirac.
Blood and saliva will be collected from each trial participant to best understand mechanisms by which Truvada or Marovirac may provide benefit. Analyses include:
Measurement of SARS-CoV-2 antibody responses, RNA, and proteins (spike, N etc).
Measurement of salivary Epstein Barr Virus load, as well as plasma quantification of antibody responses to EBV antigens.
Measurement of Human Endogenous Retrovirus (HERV) elements including bulk RNA sequencing to determine ERB expression levels from whole blood.
Deep immune profiling, including measurement of cytokines and vascular measures.
Measurement of hormones levels.
Measurement and “score” of vascular and endothelial health via EndoPAT.