Impact of Long-term Protease Inhibitors in Patients Living With HIV on the Incidence of COVID-19 ( COVIP )

Study Overview
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Brief Summary
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This is a prospective multicenter cohort study. The question arises as to whether treatment with protease inhibitors (PIs) could have a preventive role for COVID-19 infection, especially since patients living with HIV (PLWHIV) have not been described as more at risk of developing COVID-19 infection. The aim of our study will therefore be to assess the impact of long-term protease inhibitors in PLWHIV on the incidence of COVID-19.

Detailed Description
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The symptomatic management of COVID-19 infections is currently at the forefront. The therapeutic efficacy of certain molecules is being evaluated in studies, in vitro and in vivo, such as remdesivir, hydroxychloroquine / chloroquine, and lopinavir / ritonavir. The latter has been used in the treatment of HIV for many years, like other PIs such as darunavir and atazanavir. In France, around 11% of PLWHIV are treated with long-term PIs. Lopinavir / ritonavir has an inhibitory role on the protein endopeptidase of coronavirus C30 (CEP_C30). In humans, Cao et al did not demonstrate any superiority of efficacy of lopinavir / ritonavir compared to the control group receiving standard care (HR for clinical improvement: 1.24 (0.90-1, 72)), but the initiation of treatment in the study was mainly at late stages. Early initiation of lopinavir/r at the onset of SARS symptoms appears to be more effective. To our knowledge, the other PIs are under study, with a possible inhibition of the proteases of type-3-chemotrypsin or of the papain type of SARS-Cov2. Three open randomized studies in humans are underway in China, Spain, and Thailand. The question arises as to whether treatment with PIs could have a preventive role for COVID-19 infection, especially since PLWHIV have not been described as more at risk of developing COVID-19 infection. The aim of our study will therefore be to assess the impact of long-term protease inhibitors in PLWHIV on the incidence of COVID-19. This is a prospective multicenter cohort study. A random sample of 794 eligible individuals will be recruited from April 2020, consisting of 397 patients in the long-term PIs group and 397 patients in the long-term ARV regimen without PIs. The study will be offered to PLWHIV in Île-de-France, treated with long-term antiretroviral drugs with or without protease inhibitors. For those who accept: i) they will receive phone calls (teleconsultation) to collect information regarding symptoms at M0, M1 and between M3 and M6 by a medical or paramedical person from their hospital center ; ii) in case of a high probability of infection with Covid-19, an on-site consultation will be offered to them, with a diagnostic test by PCR on a nasopharyngeal swab and eventually a chest scanner if indicated ; iii) a serology on a blood sample will be performed at the end of the epidemics to look for anti-COVID-19 antibodies.

Official Title
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Prospective Description Study of the Impact of Long-term Protease Inhibitors in Patients Living With HIV on the Incidence of COVID-19

Conditions
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HIV Patients

Intervention / Treatment
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* Other: No intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV patients over 18 years of age Follow-up for an HIV infection 1 or 2 Treated with antiretroviral drugs Resident in France during the epidemics No change in antiretroviral drugs during the epidemics No-opposition to participate to the research Exclusion Criteria: Patients under guardianship or curators Opportunistic classifying pathologies by the Control Disease Center (CDC) Patients unable to give a free and informed no-opposition consent to participate to the protocol Patients under safeguarding justice

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Protease inhibitor exposed<br>HIV patients treated with antiretroviral drugs including a protease inhibitor | Other: No intervention<br>* No intervention: Usual care for nasopharyngeal sampling and blood sampling for COVID-19 detection<br>|
| Protease inhibitor non exposed<br>HIV patients treated with antiretroviral drugs without a protease inhibitor | Other: No intervention<br>* No intervention: Usual care for nasopharyngeal sampling and blood sampling for COVID-19 detection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of the incidence of COVID-19 infection in PLWHIV treated with long-term antiretroviral drugs including a protease inhibitor and those without a protease inhibitor | Occurrence of COVID-19 infection during the epidemics (M0, M1) in both study groups | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of the seroprevalence of COVID-19 infection in both groups of the study | Percentage of positive serological tests at the end of the epidemics in both study groups | 6 months | 
| Comparison of the severity of COVID-19 infection symptoms in both groups of the study. | Proportion of severe forms in both study groups | 6 months | 
| Identification of potential risk factors for COVID-19 infection in HIV patients treated with protease inhibitor or without protease inhibitor | Statistical association between a risk factor and the occurrence of COVID-19 infection in both study groups | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Protease inhibitor, antiretroviral drug, COVID-19