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HIV-1 & Coronavirus-Coinfection in Europe: Morbidity & Risk Factors of COVID-19 in People Living With HIV

Completed
Conditions
HIV-1-infection
COVID-19
Interventions
Other: COVID-19
Other: HIV-1 infection
Registration Number
NCT05481216
Lead Sponsor
NEAT ID Foundation
Brief Summary

HIV CoCo is a European multi-centre, multi-country, retrospective, observational case-control study that will aim to describe clinical outcomes and identify risk factors for People Living With HIV (PLWHIV) who are co-infected with the SARS-CoV-2 coronavirus.

The study will address two central questions:

1. Is there a particular risk for COVID-19 in PLWHIV as compared to HIV seronegative control COVID-19 cases?

2. Are there particular factors, within the group of PLWHIV, which put them at risk for a more severe COVID-19 disease course?

The study will address these questions by recruiting patients co-infected with both HIV and SARS-CoV-2 and comparing them to two control groups - one group infected with SARS-CoV-2 only and another group infected with HIV only. Only deidentified, real-world retrospective data will be used for the study, collected as part of standard, routine clinical care.

Additionally, this study will also look to:

1. Describe the differences in the clinical manifestation of COVID-19 in PLWHIV compared to HIV seronegative controls

2. Describe the response to treatment, including supportive care and novel therapies against COVID-19, including antiviral or immunomodulatory therapy

3. Describe the co-morbidities in PLWHIV and controls with COVID-19

4. Compare the severity of COVID-19 between PLWHIV and the COVID-19 only controls at diagnosis and hospital admission.

Data will be collected about patient outcomes from COVID-19 (including hospitalisation for COVID-19, length of stay in hospital, critical care admission, ventilation/oxygenation requirements, and need for kidney replacement therapy), as well as pre-existing health conditions, and relevant blood results at COVID-19 diagnosis.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
2598
Inclusion Criteria
  • • Cases (PLWHIV + COVID-19)

    1. Any gender

    2. At least 18 years of age

    3. Documented HIV-1 infection

    4. Confirmed SARS-CoV-2 infection by documented, or patient-reported, positive result on PCR testing of a nasopharyngeal or respiratory sample, before 1st April 2021

      • Controls (COVID-19)
    <!-- -->
    1. Any gender
    2. At least 18 years of age
    3. No documented HIV-1 infection
    4. Confirmed SARS-CoV-2 infection by documented, or patient-reported, positive result on PCR testing of a nasopharyngeal or respiratory sample, before 1st April 2021
    5. Meet the matching criteria

For comparing PLWHIV & COVID-19 versus HIV seronegative COVID-19 patients, a 1:1 matching will be performed according to the following criteria:

  • Age (+/- 5 years)

  • Sex

  • Ethnicity (where available)

  • Month of COVID-19 diagnosis (+/- 2 months)

  • COVID-19 diagnosis inpatient OR

  • COVID-19 diagnosis outpatient (ambulatory)

  • Controls (PLWHIV)

    1. Any gender
    2. At least 18 years of age
    3. Documented HIV-1 infection
    4. No evidence of SARS-CoV-2 infection
    5. Meet the matching criteria

For comparing PLWHIV & COVID-19 versus PLWHIV without COVID-19, a 1:2 matching for similar risk of acquiring COVID-19 will be performed according to the following criteria:

  • Age (+/- 5 years)
  • Sex
  • Ethnicity (where available)

Exclusion Criteria

For cases (PLWHIV + COVID-19) and for COVID-19 only controls:

  • COVID-19 diagnosed based on clinical criteria
Exclusion Criteria

Not provided

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
PLWHIV with COVID-19 casesHIV-1 infectionPatients who are at least 18 years of age with documented HIV-1 infection and confirmed SARS-CoV-2 infection by documented, or patient-reported, positive result on PCR testing of a nasopharyngeal or respiratory sample, before 1st April 2021.
HIV seronegative patients with COVID-19 controlsCOVID-19Patients at least 18 years of age with confirmed SARS-CoV-2 infection by documented, or patient-reported, positive result on PCR testing of a nasopharyngeal or respiratory sample, before 1st April 2021.
PLWHIV with COVID-19 casesCOVID-19Patients who are at least 18 years of age with documented HIV-1 infection and confirmed SARS-CoV-2 infection by documented, or patient-reported, positive result on PCR testing of a nasopharyngeal or respiratory sample, before 1st April 2021.
PLWHIV without COVID-19 controlsHIV-1 infectionPatients at least 18 years of age with documented HIV-1 infection.
Primary Outcome Measures
NameTimeMethod
Number of Composite Primary End Point (Critical Care Admission, Palliative Discharge When Discharged From Hospital, or Mortality Within the 6 Weeks After Diagnosis of COVID-19) EventsFrom baseline (diagnosis of COVID-19) to Week 6

The primary endpoint is a composite of the number of critical care admission (high dependency unit or intensive care unit), mortality in hospital or palliative discharge when discharged from hospital, or mortality at 6 weeks after diagnosis of COVID-19 or at discharge from hospital (where applicable) events. Time-to-event methods, including Kaplan-Meier survival curves and Cox proportional-hazards models, will be used for this analysis. The time to the primary endpoints will be defined as:

* For participants admitted to critical care Time = \[Date of Critical care admission - Date of positive PCR test for COVID-19\] + 1

* For participants admitted to critical care before diagnosis of COVID-19, Time=1 day.

* For participants with palliative discharge when discharged from hospital Time = \[Date of discharge from hospital to palliative care - Date of positive PCR test for COVID-19\] + 1.

* For participants died Time = \[Date of death - Date of positive PCR test for COVID-19\] + 1.

Kaplan-Meier Estimate of Primary End PointFrom Baseline (diagnosis of COVID-19 ) to week 6

Kaplan-Meier estimate of the composite number of critical care admission, palliative discharge and death events

Number of Palliative DischargeBaseline (diagnosis of COVID-19) to week 6

Number of palliative discharge at discharge from hospital following hospitalisation for COVID-19 events

MortalityBaseline (diagnosis of COVID-19) to week 6

Mortality at 6 weeks after diagnosis of COVID-19 or at discharge from hospital

Number of Critical Care Admission EventsBaseline (diagnosis of COVID-19) to week 6

Number of admission events to a high dependency unit or intensive care unit

HIV Viral LoadBaseline(Last CD4 cell count and HIV-RNA before COVID-19 diagnosis, or most recent for PLHIV without COVID-19)

Identification of risk factors for COVID-19 infection within the group of PLHIV: HIV viral load

Time Since HIV DiagnosisBaseline(Last CD4 cell count and HIV-RNA before COVID-19 diagnosis, or most recent for PLHIV without COVID-19)

Identification of risk factors for COVID-19 infection within the group of PLHIV: Time since HIV diagnosis

Chronic Obstructive Pulmonary DiseaseBaseline(Last CD4 cell count and HIV-RNA before COVID-19 diagnosis, or most recent for PLHIV without COVID-19)

Identification of risk factors for COVID-19 infection within the group of PLHIV: Chronic Obstructive Pulmonary Disease

CD4 Cell CountBaseline(Last CD4 cell count and HIV-RNA before COVID-19 diagnosis, or most recent for PLHIV without COVID-19)

Identification of risk factors for COVID-19 infection within the group of PLHIV: CD4 cell count

Chronic Kidney DiseaseBaseline(Last CD4 cell count and HIV-RNA before COVID-19 diagnosis, or most recent for PLHIV without COVID-19)

Identification of risk factors for COVID-19 infection within the group of PLHIV: Chronic Kidney Disease

Body WeightBaseline(Last CD4 cell count and HIV-RNA before COVID-19 diagnosis, or most recent for PLHIV without COVID-19)

Identification of risk factors for COVID-19 infection within the group of PLHIV: Body weight

Secondary Outcome Measures
NameTimeMethod
Number of Hospitalisation EventsBaseline (diagnosis of COVID-19) to week 6

Number of hospital admission for COVID-19 events

Length of Hospital StayBaseline (diagnosis of COVID-19) to week 6

Length of stay in hospital following hospitalisation for COVID-19

Length of Stay in ICUBaseline (diagnosis of COVID-19) to week 6

Median Length of Stay in Intensive Care Unit

Ventilator-free Days (VFDs)6 weeks after diagnosis of COVID-19

Number of ventilator-free days

Extracorporeal Membrane Oxygenation (ECMO)Baseline (diagnosis of COVID-19) to week 6

Length of extracorporeal membrane oxygenation

Need for Kidney Replacement TherapyBaseline(diagnosis of COVID-19) to week 6

The number of patients requiring kidney replacement therapy

Measurement of Total Comorbidity Burden6 weeks after diagnosis of COVID-19

Charlson Comorbidity Index predicts the ten-year mortality for a patient who may have a range of comorbid conditions. Index consists of 19 conditions, each with an assigned weight from 1 to 6 according to the relative risk of dying. The total score is derived by summing up the weights of comorbid conditions presented. Based on the CCI score, the severity of comorbidity was categorized into three grades: mild, with CCI scores of 1-2; moderate, with CCI scores of 3-4; and severe, with CCI scores ≥5. The minimum score value is 0 and maximum is 37. A higher score means a more greater mortality risk.

Estimate Risk of 30-day Mortality After COVID-19 InfectionBaseline (diagnosis of COVID-19) to week 6

Estimate risk of 30-day mortality after COVID-19 infection using pre-COVID health status (estimated using the Veterans Health Administration COVID-19 (VACO) index). The VACO index is expressed as a percentage and calculated based on age, sex, Charlson comorbidity index (CCI), and the presence of myocardial infarction (MI) or peripheral vascular disease (PVD). The index range is from 0.2 to 48.0. A higher score means a greater risk of mortality.

Blood Cell Counts at COVID-19 DiagnosisBaseline (Diagnosis of COVID-19)

The endpoint is the blood cell counts at COVID-19 diagnosis. The analyses will be performed with all PLHIV with COVID-19 and matched HIV-uninfected individual with COVID-19 who have data regarding the blood cell count of interest at COVID-19 diagnosis

Liver Function and Tissue Damage Parameters at COVID-19 DiagnosisBaseline(COVID-19 diagnosis)

The endpoint is the liver function (ALT, AST) and tissue damage (lactate dehydrogenase) parameters at COVID-19 diagnosis.

Inflammatory Markers and Kidney Function TestsBaseline (COVID-19 Diagnosis)

Inflammatory markers and Kidney Function tests at COVID-19 diagnosis

Biological Parameters at COVID-19 DiagnosisBaseline(COVID-19 diagnosis)

Biological parameters (D-dimer and Ferritin levels) at COVID-19 diagnosis

Cholesterol, Triglyceride and Glucose LevelsBaseline(COVID-19 diagnosis)

Cholesterol, Triglyceride and Glucose levels at COVID-19 diagnosis

Red Blood Cell CountBaseline(COVID-19 Diagnosis)

Red blood cell (RBC) count at COVID-19 Diagnosis

Haemoglobin LevelsBaseline(COVID-19 diagnosis)

Haemoglobin levels at COVID-19 diagnosis

HaematocritBaseline (COVID-19 diagnosis)

Haematocrit levels at COVID-19 diagnosis

MCV LevelsBaseline(COVID-19 diagnosis)

Mean Corpuscular volume (MCV) levels at COVID-19 diagnosis

MCH LevelsBaseline(COVID-19 diagnosis)

Mean Corpuscular Haemoglobin levels at COVID-19 diagnosis

HbA1C LevelsBaseline(COVID-19 diagnosis)

Glycated Haemoglobin (HbA1C) levels at COVID-19 diagnosis

C-reactive Protein LevelsBaseline(COVID-19 diagnosis)

C-reactive protein levels at COVID-19 diagnosis

Trial Locations

Locations (23)

CHU Saint Pierre

🇧🇪

Brussels, Belgium

Hôpital Européen Marseille

🇫🇷

Marseille, France

Hôpital Saint Louis

🇫🇷

Paris, France

Hospital de la Santa Creu I Sant Pau

🇪🇸

Barcelona, Spain

Hospital Universitari de Bellvitge

🇪🇸

Barcelona, Spain

Hospital Universitario Basurto

🇪🇸

Bilbao, Spain

Hospital General Universitario de Elche

🇪🇸

Elche, Spain

Hospital Universitario San Pedro

🇪🇸

Logroño, Spain

Hospital Ramón y Cajal

🇪🇸

Madrid, Spain

Hospital Universitario 12 de Octubre

🇪🇸

Madrid, Spain

Hospital Universitario La Paz

🇪🇸

Madrid, Spain

Erasmus Medical Center

🇳🇱

Rotterdam, Netherlands

Hospital Clinic Barcelona

🇪🇸

Barcelona, Spain

Hospital Universitario Puerta de Hierro Majadahonda

🇪🇸

Majadahonda, Spain

Bradford Teaching Hospitals NHS Foundation Trust

🇬🇧

Bradford, United Kingdom

Southmead Hospital (North Bristol)

🇬🇧

Bristol, United Kingdom

University Hospitals of Derby & Burton NHS Foundation Trust

🇬🇧

Derby, United Kingdom

Brownlee Centre, Gartnavel General Hospital

🇬🇧

Glasgow, United Kingdom

Barts Health (The Royal London Hospital)

🇬🇧

London, United Kingdom

Chelsea & Westminster Hospital NHS Foundation Trust

🇬🇧

London, United Kingdom

Guy's and St Thomas' NHS Foundation Trust

🇬🇧

London, United Kingdom

King's College Hospital NHS Foundation Trust

🇬🇧

London, United Kingdom

Royal Free London NHS Foundation Trust

🇬🇧

London, United Kingdom

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