Copenhagen Co-morbidity in HIV Infection Study (COCOMO)

• Sponsor: Rigshospitalet, Denmark
• Information provided by (Responsible Party): Susanne Dam Nielsen, MD, Rigshospitalet, Denmark

Study Description

Brief Summary:

Despite efficient antiretroviral treatment for HIV infection, decrease in life expectancy remains. Excess mortality is mainly due to non-AIDS co-morbidity including cardiovascular, pulmonary, and liver related diseases. Both HIV-unrelated and HIV-related risk factors probably contribute to this pattern. At present, most evidence regarding co-morbidity in HIV infection rely on cross-study comparisons of HIV-infected persons with published population rates and few prospective studies in U.S. cohorts. Using well characterized participants from the Copenhagen General Population Study (CGPS) as controls, we aim to include >1500 HIV-infected persons in the COCOMO study to determine if co-morbidity is more prevalent or develops at a higher rate in HIV-infected persons. The study will asses 1) cardiovascular, 2) pulmonary and 3) liver-related co-morbidity using uniformly collected data in the two cohorts. The investigators aim to study the relative impact of HIV-unrelated and HIV-related factors on development of co-morbidity.

Condition or disease	Intervention/treatment
HIV; COPD; CVD; Liver Disease	Other: No intervention.

Detailed Description:

Primary hypothesis:

Cardiovascular disease:

- HIV infection is independently associated with higher prevalence of coronary atherosclerosis (assessed by CT angiography)

Obstructive pulmonary disease:

- HIV infection is independently associated with higher prevalence of COPD, and independently associated with loss of lung function

Liver disease:

- HIV infection is independently associated with liver steatosis, steatohepatitis and liver fibrosis

Lipid and fat metabolism:

- HIV infection is independently associated with alterations in adipose fat tissue and dyslipidemia

Secondary hypothesis:

Cardiovascular disease:

• Viral load and CD4 are independently associated with coronary atherosclerosis (assessed by CT angiography) in HIV-infected individuals.
• Levels of inflammatory markers can predict coronary atherosclerosis in HIV-infected individuals.
• Microbial translocation and metabolism are associated with coronary atherosclerosis in HIV-infected individuals.
• Endothelial dysfunction (assessed by arterial elastography) can predict coronary atherosclerosis in HIV-infected individuals

Obstructive pulmonary disease:

• Viral load and CD4 is independently associated with emphysema
• HIV is independently associated with pulmonary hypertension (assessed by CT angiography), and obstructive lung disease is independently associated with airway obstruction
• PCP colonization in HIV infected patients is independently associated with obstructive lung disease, emphysema and loss of lung function.
• Inflammatory markers in HIV infected patients are associated with obstructive lung disease and loss of lung function

Study Design

• Study Type: Observational
• Estimated Enrollment: 1500 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Copenhagen Co-morbidity in HIV Infection Study
• Study Start Date: March 2015
• Estimated Primary Completion Date: March 2025
• Estimated Study Completion Date: March 2025

Groups and Cohorts

Group/Cohort	Intervention/treatment
HIV infected; Exposure to: Computed tomography(CT) of chest and upper abdomen, CT angiography(CTa) of heart, spirometry, mouth wash, eNO assessment, ankle brachial pressure index, fibroscan, blood sampling	Other: No intervention.
HIV uninfected; Exposure to: Computed tomography(CT) of chest and upper abdomen, CT angiography(CTa) of heart, spirometry, eNO assessment, ankle brachial pressure index, blood sampling	Other: No intervention.

Outcome Measures

Primary Outcome Measures :

1. Coronary atherosclerosis [ Time Frame: Baseline cross-sectional data and after 2 years follow-up ]
   Prevalence of coronary atherosclerosis; electrocardiographic abnormalities and peripheral artery disease
2. Obstructive pulmonary disease [ Time Frame: Baseline cross-sectional data and after 2 years follow-up ]
   Emphysema, airflow limitation,
3. Liver disease [ Time Frame: Baseline cross-sectional data and after 2 years follow-up ]
   Prevalence of hepatic steatosis, steatohepatitis and liver fibrosis
4. Lipid and fat metabolism [ Time Frame: Baseline cross-sectional data and after 2 years follow-up ]
   Visceral adipose tissue, dyslipidemia, gut microbiota
5. Inflammation and clonal hematopoiesis [ Time Frame: Baseline cross-sectional data and after 2 years follow-up ]
   Cytokines (e.g. IL-6, TNF-alfa), cell subsets (e.g. Tregs, Th17)

Secondary Outcome Measures :

1. Emphysema, P. jirovecii colonization [ Time Frame: Baseline data(cross-sectional data) ]
   Secondary pulmonary outcome measures
2. Depression [ Time Frame: Baseline data (cross-sectional data) ]
   Major Depression Inventory Score, kynurenin/tryptophan ratio
3. Bone metabolism [ Time Frame: Baseline data(cross-sectional data) assessed after two years ]
   Bone mineral density
4. Hematological abnormalities [ Time Frame: Baseline data(cross-sectional data) ]
   Anemia, trombocytopenia, leukopenia
5. Renal function [ Time Frame: Baseline data(cross-sectional data) ]
   Kidney function

Biospecimen Retention:   Samples With DNA

Routine biochemistry, whole blood, plasma, peripheral blood mononuclear cells (PBMCs), DNA and RNA from buffy coat, plasma, and red blood cells (RBC).

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

HIV infected patients.

Criteria

Inclusion Criteria:

• signed informed consent
• patients that are unable to understand information material
• HIV infected

Exclusion Criteria:

Computed tomography(CT):

• contraindications to CT and contrast (i.e. pregnancy, renal impairment, allergy to contrast media, allergy or contraindication to beta blocking agent, body weight more than 120kg, evidence of ongoing myocardial ischemia, heart rhythm precluding EKG gating)

Spirometry:

• relative contraindications to spirometry (i.e. chest, abdominal or eye surgery within the 3 months before baseline spirometry, and known retinal detachment)
• allergy or contraindications to salbutamol (i.e. >110 bpm, or a known uncontrolled cardiac condition (i.e. unstable coronary artery disease, decompensated heart failure)
• a respiratory illness with at least two symptoms of breathlessness, cough, wheezing, or increase in sputum production within 6 weeks.

MRI:

• Implants (e.g. pacemaker, coclea implants, insulin pumps)
• Claustrophobia
• Pregnancy

Liver Biopsy:

• Risk of bleeding
• Infection in puncture site

Contacts and Locations

Locations

Denmark

University Hospital of Copenhagen

Copenhagen, Denmark, 2100

Sponsors and Collaborators

Rigshospitalet, Denmark

Investigators

• Study Director: Andreas Ronit, MD; Department of Infectious Diseases
• Study Director: Ditte M Kirkegaard-Klitbo, MD; Department of Infectious Diseases
• Study Director: Marco Gelpi, MD; Department of Infectious Diseases
• Study Director: Andreas D Knudsen, MD; Department of Infectious Diseases
• Study Director: Rebekka Faber, MD; Department of Infectious Diseases

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ronit A, Lundgren J, Afzal S, Benfield T, Roen A, Mocroft A, Gerstoft J, Nordestgaard BG, Vestbo J, Nielsen SD; Copenhagen Co-morbidity in HIV infection (COCOMO) study group. Airflow limitation in people living with HIV and matched uninfected controls. Thorax. 2018 May;73(5):431-438. doi: 10.1136/thoraxjnl-2017-211079. Epub 2018 Jan 13.

Ronit A, Kristensen T, Klitbo DM, Gelpi M, Kalhauge A, Benfield T, Gerstoft J, Lundgren J, Vestbo J, Kofoed KF, Nielsen SD. Incidental lung cancers and positive computed tomography images in people living with HIV. AIDS. 2017 Sep 10;31(14):1973-1977. doi: 10.1097/QAD.0000000000001600.

Ronit A, Mathiesen IH, Gelpi M, Benfield T, Gerstoft J, Pressler T, Christiansen A, Lundgren J, Vestbo J, Dam Nielsen S. Small airway dysfunction in well-treated never-smoking HIV-infected individuals. Eur Respir J. 2017 Mar 2;49(3). pii: 1602186. doi: 10.1183/13993003.02186-2016. Print 2017 Mar.

Ronit A, Haissman J, Kirkegaard-Klitbo DM, Kristensen TS, Lebech AM, Benfield T, Gerstoft J, Ullum H, Køber L, Kjær A, Kofoed K, Vestbo J, Nordestgaard B, Lundgren J, Nielsen SD. Copenhagen comorbidity in HIV infection (COCOMO) study: a study protocol for a longitudinal, non-interventional assessment of non-AIDS comorbidity in HIV infection in Denmark. BMC Infect Dis. 2016 Nov 26;16(1):713.

• Responsible Party: Susanne Dam Nielsen, MD, MD, Rigshospitalet, Denmark
• ClinicalTrials.gov Identifier: NCT02382822 History of Changes
• Other Study ID Numbers: Sponsor- Rigshospitalet
• First Posted: March 9, 2015
• Last Update Posted: February 12, 2019
• Last Verified: February 2019

Additional relevant MeSH terms:

HIV Infections; Acquired Immunodeficiency Syndrome; Liver Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; Digestive System Diseases