Clinical trial NCT02382822: Copenhagen Comorbidity in HIV Infection Study
Official title: Copenhagen Comorbidity in HIV Infection Study
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: HIV
COPD
CVD
Liver Disease
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
First posted: 2015-03-09
Enrollment: 1099
Sex: ALL
Minimum age (years): 20
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: HIV infected patients.

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.

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

Eligibility criteria: Inclusion Criteria:

* signed informed consent
* HIV infected
* aged 20-100 years

Exclusion Criteria:

* patients that are unable to understand information material

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

Primary outcomes:
measure: Coronary atherosclerosis
timeFrame: Baseline cross-sectional data and after 2 years follow-up
measure: Obstructive pulmonary disease
timeFrame: Baseline cross-sectional data and after 2 years follow-up
measure: Liver disease
timeFrame: Baseline cross-sectional data and after 2 years follow-up
measure: Lipid and fat metabolism
timeFrame: Baseline cross-sectional data and after 2 years follow-up
measure: Inflammation and clonal hematopoiesis
timeFrame: Baseline cross-sectional data and after 2 years follow-up
Secondary outcomes:
measure: Emphysema, P. jirovecii colonization
timeFrame: Baseline data(cross-sectional data)
measure: Depression
timeFrame: Baseline data (cross-sectional data)
measure: Bone metabolism
timeFrame: Baseline data(cross-sectional data) assessed after two years
measure: Hematological abnormalities
timeFrame: Baseline data(cross-sectional data)
measure: Renal function
timeFrame: Baseline data(cross-sectional data)
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Copenhagen University Hospital - Rigshospitalet
city: Hvidovre
country: Denmark
facility: Copenhagen University Hospital - Amager and Hvidovre
Study officials:
affiliation: Department of Infectious Diseases, Copenhagen University Hospital - Rigshospitalet
name: Susanne D Nielsen, Professor, MD, DMSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Infectious Diseases, Copenhagen University Hospital - Amager and Hvidovre
name: Thomas L Benfield, Professor, MD, DMSc
role: STUDY_DIRECTOR
affiliation: Department of Cardiology, Copenhagen University Hospital - Rigshospitalet
name: Klaus F Kofoed, Professor, MD, PhD, DMSc
role: STUDY_DIRECTOR
affiliation: Department of Cardiology, Copenhagen University Hospital - Rigshospitalet
name: Lars V Køber, Professor, MD, PhD, DMSc
role: STUDY_DIRECTOR
affiliation: Department of Clinical Biochemistry, Copenhagen University Hospital - Herlev and Gentofte
name: Børge G Nordestgaard, Professor, MD, DMSc
role: STUDY_DIRECTOR
affiliation: Department of Clinical Biochemistry, Copenhagen University Hospital - Herlev and Gentofte
name: Shoaib Afzal, Professor, MD, DMSc
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.