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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.
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:
Obstructive pulmonary disease:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
| |
| 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| No intervention. | Other |
|
| Measure | Description | Time Frame |
|---|---|---|
| Coronary atherosclerosis | Prevalence of coronary atherosclerosis; electrocardiographic abnormalities and peripheral artery disease | Baseline cross-sectional data and after 2 years follow-up |
| Obstructive pulmonary disease | Emphysema, airflow limitation, | Baseline cross-sectional data and after 2 years follow-up |
| Liver disease | Prevalence of hepatic steatosis, steatohepatitis and liver fibrosis | Baseline cross-sectional data and after 2 years follow-up |
| Lipid and fat metabolism | Visceral adipose tissue, dyslipidemia, gut microbiota | Baseline cross-sectional data and after 2 years follow-up |
| Inflammation and clonal hematopoiesis | Cytokines (e.g. IL-6, TNF-alfa), cell subsets (e.g. Tregs, Th17) | Baseline cross-sectional data and after 2 years follow-up |
| Measure | Description | Time Frame |
|---|---|---|
| Emphysema, P. jirovecii colonization | Secondary pulmonary outcome measures | Baseline data(cross-sectional data) |
| Depression | Major Depression Inventory Score, kynurenin/tryptophan ratio |
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Inclusion Criteria:
Exclusion Criteria:
Computed tomography (CT):
Spirometry:
MRI:
Liver Biopsy:
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HIV infected patients.
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| Name | Affiliation | Role |
|---|---|---|
| Susanne D Nielsen, Professor, MD, DMSc | Department of Infectious Diseases, Copenhagen University Hospital - Rigshospitalet | Principal Investigator |
| Thomas L Benfield, Professor, MD, DMSc | Department of Infectious Diseases, Copenhagen University Hospital - Amager and Hvidovre | Study Director |
| Klaus F Kofoed, Professor, MD, PhD, DMSc | Department of Cardiology, Copenhagen University Hospital - Rigshospitalet | Study Director |
| Lars V Køber, Professor, MD, PhD, DMSc | Department of Cardiology, Copenhagen University Hospital - Rigshospitalet | Study Director |
| Børge G Nordestgaard, Professor, MD, DMSc | Department of Clinical Biochemistry, Copenhagen University Hospital - Herlev and Gentofte | Study Director |
| Shoaib Afzal, Professor, MD, DMSc | Department of Clinical Biochemistry, Copenhagen University Hospital - Herlev and Gentofte | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Copenhagen University Hospital - Rigshospitalet | Copenhagen | 2100 | Denmark | |||
| Copenhagen University Hospital - Amager and Hvidovre |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 42314937 | Derived | Heidari SL, Loft JA, Colak Y, Afzal S, Nordestgaard BG, Benfield T, Kunisaki KM, Nielsen SD, Ronit A. Prevalence and Risk Factors of Preserved Ratio Impaired Spirometry in People With HIV and Matched Population Control Participants. Chest. 2026 Jun 18:S0012-3692(26)00871-8. doi: 10.1016/j.chest.2026.05.044. Online ahead of print. | |
| 33936110 |
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| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| D008107 | Liver Diseases |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
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Routine biochemistry, whole blood, plasma, peripheral blood mononuclear cells (PBMCs), DNA and RNA from buffy coat, plasma, and red blood cells (RBC).
| Baseline data (cross-sectional data) |
| Bone metabolism | Bone mineral density | Baseline data(cross-sectional data) assessed after two years |
| Hematological abnormalities | Anemia, trombocytopenia, leukopenia | Baseline data(cross-sectional data) |
| Renal function | Kidney function | Baseline data(cross-sectional data) |
| Hvidovre |
| Denmark |
| Thudium RF, Ringheim H, Ronit A, Hoel H, Benfield T, Mocroft A, Gerstoft J, Troseid M, Borges AH, Ostrowski SR, Vestbo J, Nielsen SD. Independent Associations of Tumor Necrosis Factor-Alpha and Interleukin-1 Beta With Radiographic Emphysema in People Living With HIV. Front Immunol. 2021 Apr 14;12:668113. doi: 10.3389/fimmu.2021.668113. eCollection 2021. |
| 33493297 | Derived | Kirkegaard-Klitbo DM, Thomsen MT, Gelpi M, Bendtsen F, Nielsen SD, Benfield T. Hepatic Steatosis Associated With Exposure to Elvitegravir and Raltegravir. Clin Infect Dis. 2021 Aug 2;73(3):e811-e814. doi: 10.1093/cid/ciab057. |
| 29331988 | Derived | 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. |
| 28857778 | Derived | 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. |
| 28254767 | Derived | 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):1602186. doi: 10.1183/13993003.02186-2016. Print 2017 Mar. No abstract available. |
| 27887644 | Derived | Ronit A, Haissman J, Kirkegaard-Klitbo DM, Kristensen TS, Lebech AM, Benfield T, Gerstoft J, Ullum H, Kober L, Kjaer 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. doi: 10.1186/s12879-016-2026-9. |
| D020969 |
| Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D004066 | Digestive System Diseases |