Changes in Weight, Body Composition and Cardiac Risk After Discontinuing Abacavir Treatment in HIV-infected Individuals

Study Overview
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Brief Summary
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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
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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.

Official Title
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Changes in Weight and Body Composition After Switch to Dolutegravir/Lamivudine Compared to Continued Dolutegravir/Abacavir/Lamivudine for Virologically Suppressed HIV Infection: A Randomized Open-label Superiority Trial: AVERTAS-1

Conditions
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Hiv, HIV Infections, HIV Cardiomyopathy, Weight Change, Body, HIV Lipodystrophy, Cardiovascular Diseases

Intervention / Treatment
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* Drug: Dolutegravir / Lamivudine Oral Tablet


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A randomized controlled open-label superiority trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: dolutegravir/lamivudine<br>50 mg dolutegravir and 300 mg lamivudine (co-formulated) once daily for 48 weeks | Drug: Dolutegravir / Lamivudine Oral Tablet<br>* Discontinuing abacavir by switching from three-drug regimen with dolutegravir/abacavir/lamivudine to two-drug regimen with dolutegravir/lamivudine<br>* Other names: Dolutegravir/abacavir/lamivudine;|
| No Intervention: dolutegravir/abacavir/lamivudine<br>50 mg dolutegravir, 600 mg abacavir and 300 mg lamivudine (co-formulated) once daily for 48 weeks | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in body weight of ≥2 kg | Fasting body weight | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Virological control | HIV-RNA <50 copies/ml | 48 weeks | 
| Changes in self-rated health | 12-item Short Form Health Survey (SF-12). Scores from 0 (worse) to 100 (best). | 48 weeks | 
| Change in metabolism | Impaired insulin resistance and/or β-cell function determined by changes in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) | 48 weeks | 
| Changes in cardiac risk | D:A:D CVD risk score: Five and ten years predicted cardio vascular disease risk (percent) | 48 weeks | 
| Changes in carotid artery intima-media thickness (cIMT) | Measured by ultrasound. | 48 weeks | 
| Changes in Coronary artery calcium score (CACS) | Measures by CT-scan. Scores from 0 and with no upper limit. The higher score, the worse calcification/plaque level and higher CVD risk. | 48 weeks | 
| Changes in cardiac blood markers | Changes in N-terminal pro-B-type natriuretic peptide (Pro-BNP) | 48 weeks | 
| Changes in bloodpressure | Systolic and diastolic blood pressure (mmHg) | 48 weeks | 
| Changes in fat distribution VAT/SAT | Measured by CT-scan • Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) determined by abdominal CT. | 48 weeks | 
| Changes in liver stiffness | Measured by CT-scan and liver elastography | 48 weeks | 
| Changes in liver fat infiltration | Measured by CT-scan and liver elastography | 48 weeks | 
| Changes in fat distribution in trunk, limb and extremities | Measured by dual energy xray absorptiometry (DEXA) | 48 weeks | 
| Changes in inflammation | High-sensitive C-reactive protein | 48 weeks | 
| Changes in interleukins | Interleukin 1- and interleukin 6 | 48 weeks | 
| Changes in endothelial function | Vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 | 48 weeks | 
| Changes in soluble P-selectin | soluble P-selectin | 48 weeks | 
| Changes in soluble glycoprotein VI | soluble glycoprotein VI | 48 weeks | 
| Changes in d-dimer | D-dimer | 48 weeks | 
| Changes in coagulation | Factor 2, 7 and 10 (extrinsic pathway) | 48 weeks | 
| Changes in fibrinogen | Fibrinogen | 48 weeks | 
| Changes in blood Hemoglobin | Hemoglobin | 48 weeks | 
| Changes in blood platelets | Platelets | 48 weeks | 
| Changes in plasma creatinine | Creatinine | 48 weeks | 
| Changes in plasma urea | Urea | 48 weeks | 
| Changes in plasma sodium | Sodium | 48 weeks | 
| Changes in plasma potassium | Potassium | 48 weeks | 
| Changes in plasma bilirubin | Bilirubin | 48 weeks | 
| Changes in plasma alanine | Alanine | 48 weeks | 
| Changes in plasma aminotransferase | Aminotransferase | 48 weeks | 
| Cardiovascular risk | Framingham risk score: Estimated 10 years risk of cardiovascular disease (percent) | 48 weeks | 
| Cardiac biomarkers | Changes in Troponin T (TnT) | 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Weight changes, Antiretroviral Therapy, Cardiovascular disease, Antiretroviral therapy side effects, Antiretroviral two-drug regimen, HIV metabolism, HIV diabetes