How Does Antiretroviral Therapy Affect Coronary Atherosclerosis: a Serial CT Study (HART CT)

University of Liverpool

Status and phase

Withdrawn

Phase 4

Conditions

Coronary Artery Disease

Hiv

Treatments

Drug: Biktarvy

Study type

Interventional

Funder types

Other

Identifiers

NCT03986697

2017-005033-22 (EudraCT Number)

UoL001362

Details and patient eligibility

About

Combined antiretroviral therapy (cART) is thought to promote coronary artery disease via a number of mechanisms: abnormal lipid profiles, endothelial dysfunction, hypertension, insulin resistance and renal impairment are the main pathological mechanisms driving atherosclerosis as a consequence of cART. An association between protease inhibitors and increased cardiovascular disease risk has been shown in many large cohort trials.

CT Coronary Angiography (CTCA) is now widely used to assess for the presence of atherosclerosis, typically in patients presenting with chest pain. This imaging technique allows visualisation of the coronary arteries and quantification of any atherosclerotic disease that may be present. This technique is being increasingly used as a surrogate for cardiovascular disease risk.

HART CT is an open label, prospective, randomised-control pilot study to investigate the feasibility of performing a future appropriately powered multi-centred randomised control trial using CT based outcome data as a surrogate for cardiovascular disease risk.

Participants will be randomised to either continue their usual cART or switch to Biktarvy (a fixed dose combination of bictegravir, emtricitabine and tenofovir alafenamide). A baseline CT scan will be performed. If there is any evidence of atherosclerosis a further CT scan will be performed at the end of the study (approximately 48 weeks). This will allow quantification of any change in coronary artery plaque burden or characteristic. Participants will be also followed up for any changes in metabolic health.

Sex

All

Ages

40+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

HIV positive
Undetectable viral load on cART which contain protease inhibitors (duration >6 months at eligibility visit)
Age>40 years
Stable cART
No previous documented cardiovascular disease
No contraindication to study drug
Ability to give informed consent
Willingness to comply with all study requirements
No symptoms of overt cardiovascular disease

A definition of stable cART is no change to the medication regime in the preceding 6 months.

Well controlled hypertension is considered acceptable for recruitment.

Exclusion Criteria:

Active liver disease (previously diagnosed)
Renal disease eGFR <30
Any ongoing infection
Significant ionising radiation in preceding 12 months
Known or suspected cardiovascular disease
High dose statin therapy (Atorvastatin 20mg or more, Rosuvastatin 20mg or more)
Pregnancy or planned pregnancy
Breast feeding
Allergy to iodine based contrast agent
Known drug resistance to NRTI or Integrase
Any contraindication to BIC/FTC/TAF
Current enrolment onto another CTIMP.

Significant ionising radiation should not exceed >25mSv from medical sources. A definition of cardiovascular disease includes documented angina, previous myocardial infarction or previous coronary revascularization.