Changes in weight, body composition and metabolic parameters after switch to dolutegravir/lamuvidine compared to continued treatment with dolutegravir/abacavir/lamuvidine for virologically suppressed HIV infection: A randomized open-label superiority trial. The AVERTAS-1 trial

INTERVENTION:

Trade Name: Triumeq Pharmaceutical Form: Tablet CAS Number: 188062‐50‐2 Other descriptive name: ABACAVIR SULFATE Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 600‐ Other descriptive name: DOLUTEGRAVIR SODIUM Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 50‐ INN or Proposed

INN:

LAMIVUDINE CAS Number: 134678‐17‐4 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 300‐ Trade Name: Dovato Pharmaceutical Form: Tablet Other descriptive name: DOLUTEGRAVIR SODIUM Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 50‐ INN or Proposed

INN:

LAMIVUDINE CAS Number: 134678‐17‐4 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 300‐

CONDITION:

Human immunodeficiency viruses (HIV) ; MedDRA version: 21.1 Level: PT Classification code 10067326 Term: Antiretroviral therapy System Organ Class: 10042613 ‐ Surgical and medical procedures Therapeutic area: Diseases [C] ‐ Virus Diseases [C02]

PRIMARY OUTCOME:

Main Objective: The aim of this study is to investigate if discontinuing abacavir by switching from a 3 drug regimen with with dolutegravir /abacavir/lamivudine to a 2 drug regimen with dolutegravir/lamivudine will cause changes in weight, and in metabolic and cardiac parameters in individuals infected with HIV. Primary end point(s): Primary outcome is defined by changes in body weight of more than 2 kg from baseline to week 48. Secondary Objective: Not applicable Timepoint(s) of evaluation of this end point: 48 weeks

SECONDARY OUTCOME:

Secondary end point(s): Safety; Virological control at 48 weeks of follow up as defined by a plasma HIV‐RNA <50 copies/ml; ; Selfrated health; • 12‐Item Short Form Survey (SF‐12); ; Metabolism; • Development of metabolic syndrome or diabetes; • Impaired insulin resistance and/or ß‐cell function determined by changes in HOMA‐IR; Changes in:; • Framingham Risk Score; • HbA1c, cholesterol total, HDL, LDL, VLDL, triglycerides; • Fat distribution evaluated as; o Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) determined by abdominal CT; o Hepatic steatosis: Development of steatosis or increase in steatosis from baseline (CT and liver elastography); o Fat distribution in trunk, limb and extremities measured by DEXA; ; ; Cardiac; Changes in from baseline to week 48 in:; • Blood pressure and pulse; • Cardiac magnetic resonance imaging (MRI); • Carotid artery intima‐media thickness (cIMT) measured by ultra sound; • Coronary artery calcium score (CACS); • N‐terminal pro‐B‐type natriuretic peptide (Pro‐BNP), Troponin T (TnT); ; Inflammation, endothelial function, platelet function and coagulation; Changes in from baseline to week 48 in:; • Inflammation: High‐sensitive C‐reactive protein, interleukin 1‐ and 6.; • Endothelial function: Vascular cell adhesion molecule 1 and intercellular adhesion molecule 1.; • Platelet function: soluble P‐selectin and soluble glycoprotein VI.; • Coagulation: D‐dimer, factor 2, 7 and 10 (extrinsic pathway) and fibrinogen; • General: Leucocytes, hemoglobin, platelets, creatinine, urea, sodium, potassium, bilirubin, alanine aminotransferase.; Timepoint(s) of evaluation of this end point: 48 weeks

INCLUSION CRITERIA:

‐ Individuals = 18 years old with ‐ Diagnosed HIV and ‐ At least 6 months of ongoing treatment with dolutegravir/ abacavir/lamivudine prior to inclusion ‐ No pre‐existing viral resistance mutations to lamivudine or to dolutegravir ‐ Plasma viral load (HIV‐RNA) < 50 copies/ml Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 84 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range