- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04526977
Differences in Immune Response Among HIV-1-infected Individuals With Previous or Current COVID-19 (CoVIHDis). (CoVIHDis)
Differences in Susceptibility and Cytokine Profile, Specific CD4/CD8 T Cell Response, Toll Like Receptors (TLRs) and Killer Immunoglobulin-like Receptors (KIRs) Among HIV-1-infected Individuals With Previous or Current COVID-19
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Since March 2020, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has affected almost five million people in 168 countries on five continents, with more than 300.000 deaths (1-4). The scientific evidence so far does not suggest that people with HIV-1 have an increased risk of serious complications if they develop COVID-19 disease (5-7). In our recent work, we have shown in a few patients that people with HIV-1 under antiretroviral treatment, with undetectable viral load and a CD4 count greater than 200 cells/mm3, do not have a higher risk of developing serious complications than people without HIV-1, but also HIV-1 infected patients does not seem to be protected of the so-called cytokine storm (8-11). Like in the general population, they would be more likely to develop serious complications if they are older and with previous pathologies (comorbidity), such as high blood pressure, diabetes, cardiovascular disease, chronic lung disease, cancer or immunosuppression (congenital, acquired or due to treatment with immunosuppressive drugs). Thus, people with HIV-1 who are immunocompromised with a CD4 count less than 200 cells/mm3, regardless of whether or not they take antiretroviral treatment should be considered among the vulnerable groups and therefore at an increased risk of developing serious clinical complications associated to COVID-19 (12-14). It should be noted, however, that, so far, there is no enough scientific evidence that can confirm this possibility (10,15-17).
Since March 2020, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has affected almost five million people in 168 countries on five continents, with more than 300.000 deaths (1-4). The scientific evidence so far does not suggest that people with HIV-1 have an increased risk of serious complications if they develop COVID-19 disease (5-7). In our recent work, we have shown in a few patients that people with HIV-1 under antiretroviral treatment, with undetectable viral load and a CD4 count greater than 200 cells/mm3, do not have a higher risk of developing serious complications than people without HIV-1, but also HIV-1 infected patients does not seem to be protected of the so-called cytokine storm (8-11). Like in the general population, they would be more likely to develop serious complications if they are older and with previous pathologies (comorbidity), such as high blood pressure, diabetes, cardiovascular disease, chronic lung disease, cancer or immunosuppression (congenital, acquired or due to treatment with immunosuppressive drugs). Thus, people with HIV-1 who are immunocompromised with a CD4 count less than 200 cells/mm3, regardless of whether or not they take antiretroviral treatment should be considered among the vulnerable groups and therefore at an increased risk of developing serious clinical complications associated to COVID-19 (12-14). It should be noted, however, that, so far, there is no enough scientific evidence that can confirm this possibility (10,15-17).
Indeed, there are two main questions for the management of this disease in this population, the real incidence of COVID 19 (susceptibility) and if the immune response could be different in those who were already coinfected.
- The differences in susceptibility to infection could be related to host factors. Thus, it is important to characterize and genotyping the main receptor for SARS-CoV-2, ACE2, and other related receptor, such as CD26, to explore the genetic background affecting the real incidence of this disease, along CD4 count and antiretroviral therapy.
- People with HIV-1 have an impaired immune system, especially in those with less than 200 CD4 cells/mm3. Hence, the immune response in these individuals could be weaker than in general population, including the cytokine response reported after SARS-CoV-2 infection (18-20). In addition, the specific CD4/CD8 T cell response could be altered due to the HIV-1 infection and the level of immunosuppression. This specific T cell response could be a good marker for the presence or persistence of immunity against SARS-CoV-2 infections.
In addition, the first line of immune defense is the interaction of the virus with innate immunity cell members. The toll like receptors (TLRs) family is a group of pattern recognition receptors that include many different molecules (21-23). These bindings can activate dendritic cells, monocytes, macrophages. There is an important RNA and DNA connection, activation of TLRs, the production of type I interferons, and the development of some autoimmune diseases. TLR7 and TLR8 specifically recognize simple-chain RNA of viruses and are expressed in endosomal membranes. TLR8 is expressed in regulatory cells (Treg) and its activation results in inhibition of its regulatory functions. Natural killer cells (NK) respond to alterations of class I HLA molecules present in infected cells (24-26). An increase in class I HLA expression could lead to an increase in NK activation by increasing its ability to produce IFN-gamma. Therefore, the reasons for KIR binding are often variable between individuals and between populations. However, there are no data about TLRs activation and KIRs binding in HIV infected patients with SARS CoV-2 infection.
This project is designed to improve scientific knowledge and give answers to the actual clinical questions regarding SARS-CoV-2 infection in people living with HIV-1. It could be of importance to determine the risk of infection not related to HIV-related factors, and to ascertain the adequation of the immune response of HIV infected patients after a SARS-CoV-2, identifying therefore those at risk of severe disease.
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Contact
- Name: Jose L Casado, PhD
- Phone Number: 0034913368672
- Email: jcasado.hrc@salud.madrid.org
Study Contact Backup
- Name: Alejandro Vallejo, PhD
- Phone Number: 0034913368710
- Email: avallejot@gmail.com
Study Locations
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-
-
Madrid, Spain, 28034
- Recruiting
- Hospital Ramon Y Cajal
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Contact:
- Jose L Casado, Md, PhD
- Phone Number: 34913368790
- Email: jcasado.hrc@salud.madrid.org
-
Sub-Investigator:
- Alejandro Vallejo, MD, PhD
-
Sub-Investigator:
- Pilar Vizcarra, MD
-
Sub-Investigator:
- Carmen Quereda, MD, PhD
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Sub-Investigator:
- Ana Moreno, MD, PhD
-
Sub-Investigator:
- Jose M Del Rey, MD, PhD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- adult (>18 year-old), confirmed HIV-1-infection, and provide written informed consent, with previous SARS CoV-2 infection as demonstrated by clinical and a positive PCR (cases) or no previous compatible symptoms and no diagnosis of SARS-CoV-2 infection (controls, classified according to serological determination)
Exclusion Criteria:
- unable to provide a written informed consent.
- immunological alterations (chronic intake of corticoid or immunosuppresants)
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Cases
HIV-1 infected individuals with previous or current diagnosis of SARS-CoV-2 infection, defined as the presence of suggestive symptoms and a positive PCR from the nasopharyngeal swab.
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Controls
HIV-1-infected individuals of the same age (range, 5 years) and sex, who not have been diagnosed of clinical (asymptomatic) or confirmed SARS CoV-2 infection, but were positive for IgG antibodies (controls group 1) or with no evidence of SARS-CoV-2 infection (no previous neither current symptoms, negative for IgM/IgG antibodies, controls group 2)
|
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes in immune cellular response
Time Frame: 3 months
|
Differences in cellular response to SARS-COV-2 peptides
|
3 months
|
Collaborators and Investigators
Investigators
- Principal Investigator: Jose L Casado, PhD, Hospital Ramon Y Cajal
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- EC 273/20
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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