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

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.

Study Overview

• Status: Completed
• Conditions: COVID-19; HIV-1-infection
• Intervention / Treatment: Other: COVID-19; Other: HIV-1 infection

• Study Type: Observational
• Enrollment (Actual): 2598

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium
    • CHU Saint Pierre
• France
  • Marseille, France
    • Hôpital Européen Marseille
  • Paris, France
    • Hopital Saint Louis
• Netherlands
  • Rotterdam, Netherlands
    • Erasmus Medical Center
• Spain
  • Barcelona, Spain
    • Hospital de la Santa Creu i Sant Pau
  • Barcelona, Spain
    • Hospital Universitari de Bellvitge
  • Barcelona, Spain
    • Hospital Clinic Barcelona
  • Bilbao, Spain
    • Hospital Universitario Basurto
  • Elche, Spain
    • Hospital General Universitario de Elche
  • Logroño, Spain
    • Hospital Universitario San Pedro
  • Madrid, Spain
    • Hospital Ramon y Cajal
  • Madrid, Spain
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain
    • Hospital Universitario La Paz
  • Majadahonda, Spain
    • Hospital Universitario Puerta de Hierro Majadahonda
• United Kingdom
  • Bradford, United Kingdom
    • Bradford Teaching Hospitals NHS Foundation Trust
  • Bristol, United Kingdom
    • Southmead Hospital (North Bristol)
  • Derby, United Kingdom
    • University Hospitals of Derby & Burton NHS Foundation Trust
  • Glasgow, United Kingdom
    • Brownlee Centre, Gartnavel General Hospital
  • London, United Kingdom
    • Royal Free London NHS Foundation Trust
  • London, United Kingdom
    • King's College Hospital NHS Foundation Trust
  • London, United Kingdom
    • Guy's and St Thomas' NHS Foundation Trust
  • London, United Kingdom
    • Chelsea & Westminster Hospital NHS Foundation Trust
  • London, United Kingdom
    • Barts Health (The Royal London Hospital)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population will consist of adult PLWHIV with and without COVID-19 disease, followed up at the study sites for routine clinical care. Data from adult COVID-19 patients without HIV infection will be used as controls.

500 cases (PLWHIV + COVID-19) will be recruited. These patients will be at least 18 years old with documented HIV-1 infection and SARS-CoV-2 infection by documented, or patient-reported, positive result on PCR testing of a nasopharyngeal or respiratory sample, before 1st April 2021.

500 COVID-19 controls will be recruited. These patients will be at least 18 years old without documented HIV-1 infection but 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.

1000 PLWHIV control patients will be recruited for the second control group. This group will include individuals at least 18 years old with documented HIV-1 infection.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Retrospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
PLWHIV with COVID-19 cases; Patients 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.	Other: COVID-19; Diagnosed with COVID-19 infection; Other: HIV-1 infection; Diagnosed with HIV-1 infection
PLWHIV without COVID-19 controls; Patients at least 18 years of age with documented HIV-1 infection.	Other: HIV-1 infection; Diagnosed with HIV-1 infection
HIV seronegative patients with COVID-19 controls; Patients 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.	Other: COVID-19; Diagnosed with COVID-19 infection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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) Events	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.	From baseline (diagnosis of COVID-19) to Week 6
Kaplan-Meier Estimate of Primary End Point	Kaplan-Meier estimate of the composite number of critical care admission, palliative discharge and death events	From Baseline (diagnosis of COVID-19 ) to week 6
Number of Palliative Discharge	Number of palliative discharge at discharge from hospital following hospitalisation for COVID-19 events	Baseline (diagnosis of COVID-19) to week 6
Mortality	Mortality at 6 weeks after diagnosis of COVID-19 or at discharge from hospital	Baseline (diagnosis of COVID-19) to week 6
Number of Critical Care Admission Events	Number of admission events to a high dependency unit or intensive care unit	Baseline (diagnosis of COVID-19) to week 6
HIV Viral Load	Identification of risk factors for COVID-19 infection within the group of PLHIV: HIV viral load	Baseline(Last CD4 cell count and HIV-RNA before COVID-19 diagnosis, or most recent for PLHIV without COVID-19)
Time Since HIV Diagnosis	Identification of risk factors for COVID-19 infection within the group of PLHIV: Time since HIV diagnosis	Baseline(Last CD4 cell count and HIV-RNA before COVID-19 diagnosis, or most recent for PLHIV without COVID-19)
Chronic Obstructive Pulmonary Disease	Identification of risk factors for COVID-19 infection within the group of PLHIV: Chronic Obstructive Pulmonary Disease	Baseline(Last CD4 cell count and HIV-RNA before COVID-19 diagnosis, or most recent for PLHIV without COVID-19)
CD4 Cell Count	Identification of risk factors for COVID-19 infection within the group of PLHIV: CD4 cell count	Baseline(Last CD4 cell count and HIV-RNA before COVID-19 diagnosis, or most recent for PLHIV without COVID-19)
Chronic Kidney Disease	Identification of risk factors for COVID-19 infection within the group of PLHIV: Chronic Kidney Disease	Baseline(Last CD4 cell count and HIV-RNA before COVID-19 diagnosis, or most recent for PLHIV without COVID-19)
Body Weight	Identification of risk factors for COVID-19 infection within the group of PLHIV: Body weight	Baseline(Last CD4 cell count and HIV-RNA before COVID-19 diagnosis, or most recent for PLHIV without COVID-19)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Hospitalisation Events	Number of hospital admission for COVID-19 events	Baseline (diagnosis of COVID-19) to week 6
Length of Hospital Stay	Length of stay in hospital following hospitalisation for COVID-19	Baseline (diagnosis of COVID-19) to week 6
Length of Stay in ICU	Median Length of Stay in Intensive Care Unit	Baseline (diagnosis of COVID-19) to week 6
Ventilator-free Days (VFDs)	Number of ventilator-free days	6 weeks after diagnosis of COVID-19
Extracorporeal Membrane Oxygenation (ECMO)	Length of extracorporeal membrane oxygenation	Baseline (diagnosis of COVID-19) to week 6
Need for Kidney Replacement Therapy	The number of patients requiring kidney replacement therapy	Baseline(diagnosis of COVID-19) to week 6
Measurement of Total Comorbidity Burden	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.	6 weeks after diagnosis of COVID-19
Estimate Risk of 30-day Mortality After COVID-19 Infection	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.	Baseline (diagnosis of COVID-19) to week 6
Blood Cell Counts at COVID-19 Diagnosis	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	Baseline (Diagnosis of COVID-19)
Liver Function and Tissue Damage Parameters at COVID-19 Diagnosis	The endpoint is the liver function (ALT, AST) and tissue damage (lactate dehydrogenase) parameters at COVID-19 diagnosis.	Baseline(COVID-19 diagnosis)
Inflammatory Markers and Kidney Function Tests	Inflammatory markers and Kidney Function tests at COVID-19 diagnosis	Baseline (COVID-19 Diagnosis)
Biological Parameters at COVID-19 Diagnosis	Biological parameters (D-dimer and Ferritin levels) at COVID-19 diagnosis	Baseline(COVID-19 diagnosis)
Cholesterol, Triglyceride and Glucose Levels	Cholesterol, Triglyceride and Glucose levels at COVID-19 diagnosis	Baseline(COVID-19 diagnosis)
Red Blood Cell Count	Red blood cell (RBC) count at COVID-19 Diagnosis	Baseline(COVID-19 Diagnosis)
Haemoglobin Levels	Haemoglobin levels at COVID-19 diagnosis	Baseline(COVID-19 diagnosis)
Haematocrit	Haematocrit levels at COVID-19 diagnosis	Baseline (COVID-19 diagnosis)
MCV Levels	Mean Corpuscular volume (MCV) levels at COVID-19 diagnosis	Baseline(COVID-19 diagnosis)
MCH Levels	Mean Corpuscular Haemoglobin levels at COVID-19 diagnosis	Baseline(COVID-19 diagnosis)
HbA1C Levels	Glycated Haemoglobin (HbA1C) levels at COVID-19 diagnosis	Baseline(COVID-19 diagnosis)
C-reactive Protein Levels	C-reactive protein levels at COVID-19 diagnosis	Baseline(COVID-19 diagnosis)

Collaborators and Investigators

• Sponsor: NEAT ID Foundation
• Collaborators: Gilead Sciences

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2022
• Primary Completion (Actual): March 31, 2023
• Study Completion (Actual): August 31, 2023

Study Registration Dates

• First Submitted: July 29, 2022
• First Submitted That Met QC Criteria: July 29, 2022
• First Posted (Actual): August 1, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 3, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19; Coinfection
• Other Study ID Numbers: 303CoCo

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Only anonymised summary-format data will be shared.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No