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

Phase 4

Completed

• Conditions: Hiv; Weight Change, Body; HIV Cardiomyopathy; HIV Lipodystrophy; HIV Infections; Cardiovascular Diseases
• Interventions: Drug: Dolutegravir / Lamivudine Oral Tablet

• Registration Number: NCT04904406
• Lead Sponsor: Thomas Benfield

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.

Study Timeline

• Study First Submitted: 2020-10-09
• Study Start: 2020-10-22
• Study First Submitted QC: 2021-05-26
• Study First Posted: 2021-05-27
• Primary Completion: 2023-12-01
• Study Completion: 2023-12-01
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-24
• Last Update Posted: 2024-05-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 81

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
dolutegravir/lamivudine	Dolutegravir / Lamivudine Oral Tablet	50 mg dolutegravir and 300 mg lamivudine (co-formulated) once daily for 48 weeks

Primary Outcome Measures

Name	Time	Method
Changes in body weight of ≥2 kg	48 weeks	Fasting body weight

Secondary Outcome Measures

Name	Time	Method
Changes in fibrinogen	48 weeks	Fibrinogen
Changes in plasma urea	48 weeks	Urea
Changes in plasma sodium	48 weeks	Sodium
Changes in plasma bilirubin	48 weeks	Bilirubin
Changes in plasma alanine	48 weeks	Alanine
Cardiovascular risk	48 weeks	Framingham risk score: Estimated 10 years risk of cardiovascular disease (percent)
Virological control	48 weeks	HIV-RNA \<50 copies/ml
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 fat distribution in trunk, limb and extremities	48 weeks	Measured by dual energy xray absorptiometry (DEXA)
Changes in d-dimer	48 weeks	D-dimer
Changes in blood Hemoglobin	48 weeks	Hemoglobin
Changes in plasma creatinine	48 weeks	Creatinine
Changes in plasma potassium	48 weeks	Potassium
Changes in bloodpressure	48 weeks	Systolic and diastolic blood pressure (mmHg)
Changes in liver fat infiltration	48 weeks	Measured by CT-scan and liver elastography
Changes in interleukins	48 weeks	Interleukin 1- and interleukin 6
Changes in soluble P-selectin	48 weeks	soluble P-selectin
Changes in soluble glycoprotein VI	48 weeks	soluble glycoprotein VI
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 liver stiffness	48 weeks	Measured by CT-scan and liver elastography
Changes in endothelial function	48 weeks	Vascular cell adhesion molecule 1 and intercellular adhesion molecule 1
Changes in coagulation	48 weeks	Factor 2, 7 and 10 (extrinsic pathway)
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 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 inflammation	48 weeks	High-sensitive C-reactive protein
Changes in blood platelets	48 weeks	Platelets
Changes in plasma aminotransferase	48 weeks	Aminotransferase
Cardiac biomarkers	48 weeks	Changes in Troponin T (TnT)

Trial Locations

Locations (2)

Copenhagen University Hospital - Rigshospitalet; 🇩🇰 Copenhagen, Denmark

Copenhagen University Hospital, Amager Hvidovre; 🇩🇰 Hvidovre, Denmark