Cardiovascular Diseases, Hiv, HIV Cardiomyopathy, HIV Infections, HIV Lipodystrophy, Weight Change, Body
Conditions
Keywords
HIV, Weight changes, Antiretroviral Therapy, Cardiovascular disease, Antiretroviral therapy side effects, Antiretroviral two-drug regimen, HIV metabolism, HIV diabetes
Brief summary
Randomized controlled parallel open-label study in people living with HIV and at least 6 month of treatment with dolutegravir/abacavir/lamivudine prior to inclusion. Participants (n=95) are randomized to continue 3 drug-regimen dolutegravir/abacavir/lamivudine (control) or switch to two-drug regimen with dolutegravir/lamivudine (intervention). Follow-up is 48 weeks. Data is collected at baseline and week 48. Primary outcome is changes in weight from baseline of more than 2 kg. Secondary outcomes are changes in cardiac risk, composition and calcification of the heart tissue, and changes in body composition and metabolism, inflammation and coagulation. A MRI substudy is applied to focus on the cardiac adverse effects of abacavir.
Detailed description
In the MRI sub study 40 patients from the main study (20 from each group) are included. A cardiac MRI are performed at baseline and week 48 to evaluate cardiac effects of abacavir.
Interventions
DRUGDolutegravir / Lamivudine Oral Tablet
Discontinuing abacavir by switching from three-drug regimen with dolutegravir/abacavir/lamivudine to two-drug regimen with dolutegravir/lamivudine
Sponsors
Thomas Benfield
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
A randomized controlled open-label superiority trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* ≥ 18 years old * Diagnosed HIV * At least 6 months of ongoing treatment with dolutegravir/ abacavir/lamivudine * Plasma viral load (HIV-RNA) \< 50 copies/ml at inclusion For women of childbearing potential: * Negative pregnancy test * Willingness to use contraceptive (consistent with local regulations) during study period
Exclusion criteria
* Pre-existing viral resistance mutations to lamivudine or to dolutegravir * Presence of hepatitis B antigen (HBsAg) or Hepatitis B virus DNA (HBV DNA) * Cancer within past 5 years * Diabetes, cardiovascular disease or other chronic illness considered stable as assessed by the treating physician For women of childbearing potential: * Pregnancy * Breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in body weight of ≥2 kg | 48 weeks | Fasting body weight |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in self-rated health | 48 weeks | 12-item Short Form Health Survey (SF-12). Scores from 0 (worse) to 100 (best). |
| Change in metabolism | 48 weeks | Impaired insulin resistance and/or β-cell function determined by changes in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) |
| Changes in cardiac risk | 48 weeks | D:A:D CVD risk score: Five and ten years predicted cardio vascular disease risk (percent) |
| Changes in carotid artery intima-media thickness (cIMT) | 48 weeks | Measured by ultrasound. |
| Changes in Coronary artery calcium score (CACS) | 48 weeks | Measures by CT-scan. Scores from 0 and with no upper limit. The higher score, the worse calcification/plaque level and higher CVD risk. |
| Changes in cardiac blood markers | 48 weeks | Changes in N-terminal pro-B-type natriuretic peptide (Pro-BNP) |
| Changes in bloodpressure | 48 weeks | Systolic and diastolic blood pressure (mmHg) |
| Changes in fat distribution VAT/SAT | 48 weeks | Measured by CT-scan • Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) determined by abdominal CT. |
| Changes in liver stiffness | 48 weeks | Measured by CT-scan and liver elastography |
| Virological control | 48 weeks | HIV-RNA \<50 copies/ml |
| Changes in fat distribution in trunk, limb and extremities | 48 weeks | Measured by dual energy xray absorptiometry (DEXA) |
| Changes in inflammation | 48 weeks | High-sensitive C-reactive protein |
| Changes in interleukins | 48 weeks | Interleukin 1- and interleukin 6 |
| Changes in endothelial function | 48 weeks | Vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 |
| Changes in soluble P-selectin | 48 weeks | soluble P-selectin |
| Changes in soluble glycoprotein VI | 48 weeks | soluble glycoprotein VI |
| Changes in d-dimer | 48 weeks | D-dimer |
| Changes in coagulation | 48 weeks | Factor 2, 7 and 10 (extrinsic pathway) |
| Changes in fibrinogen | 48 weeks | Fibrinogen |
| Changes in blood Hemoglobin | 48 weeks | Hemoglobin |
| Changes in blood platelets | 48 weeks | Platelets |
| Changes in plasma creatinine | 48 weeks | Creatinine |
| Changes in plasma urea | 48 weeks | Urea |
| Changes in plasma sodium | 48 weeks | Sodium |
| Changes in plasma potassium | 48 weeks | Potassium |
| Changes in plasma bilirubin | 48 weeks | Bilirubin |
| Changes in plasma alanine | 48 weeks | Alanine |
| Changes in plasma aminotransferase | 48 weeks | Aminotransferase |
| Cardiovascular risk | 48 weeks | Framingham risk score: Estimated 10 years risk of cardiovascular disease (percent) |
| Cardiac biomarkers | 48 weeks | Changes in Troponin T (TnT) |
| Changes in liver fat infiltration | 48 weeks | Measured by CT-scan and liver elastography |
Other
| Measure | Time frame | Description |
|---|---|---|
| Cardiac MRI substudy primary outcome (composite) ECV | 48 weeks | Cardiac MRI applied on 40 patients to evaluate: Decrease in extracellular myocardial volume (ECV) from baseline to week 48 |
| Cardiac MRI substudy primary outcome (composite) atrial volume | 48 weeks | Cardiac MRI applied on 40 patients to evaluate: Decrease in left atrial volume from baseline to week 48 |
| Cardiac MRI substudy primary outcome (composite) diastolic function | 48 weeks | Cardiac MRI applied on 40 patients to evaluate: Improvement in diastolic function from baseline to week 48 |
| Cardiac MRI substudy primary outcome (composite) myocardial mass | 48 weeks | Cardiac MRI applied on 40 patients to evaluate: Reduction in myocardial mass from baseline to week 48 |
| Cardiac MRI substudy secondary outcome ejection fraction (EF) | 48 weeks | Cardiac MRI applied on 40 patients to evaluate: Secondary outcomes Changes in: • Ejection fraction (EF) |
| Cardiac MRI substudy secondary outcome perfusion | 48 weeks | Cardiac MRI applied on 40 patients to evaluate: Secondary outcomes Changes in: • Perfusion |
| Cardiac MRI substudy secondary outcome edema/inflammation | 48 weeks | Cardiac MRI applied on 40 patients to evaluate: Secondary outcomes Changes in: • Edema/inflammation |
| Cardiac MRI substudy secondary outcome fibrosis | 48 weeks | Cardiac MRI applied on 40 patients to evaluate: Secondary outcomes Changes in: • Fibrosis |
| Cardiac MRI substudy secondary outcome lipid | 48 weeks | Cardiac MRI applied on 40 patients to evaluate: Secondary outcomes Changes in: • Lipid-water profile Measured by MR spectroscopy |
Countries
Denmark
Outcome results
None listed