Back to resultsChanges in Weight, Body Composition and Metabolic Parameters After Discontinuing Dolutegravir or Tenofovir Disproxil (AVERTAS-2)
Primary Purpose
Hiv, HIV Infections, HIV Lipodystrophy
Status
Unknown status
Phase
Phase 4
Locations
Denmark
Study Type
Interventional
Intervention
Dolutegravir/Lamivudine 50 MG-300 MG Oral Tablet [DOVATO]
Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate 100 MG-300 MG-300 MG Oral Tablet [DELSTRIGO]
Sponsored by
About this trial
This is an interventional treatment trial for Hiv focused on measuring HIV, antiretroviral therapy, antiretroviral therapy adverse events, weight gain, body composition, fat distribution
Eligibility Criteria
Inclusion Criteria:
- Individuals ≥ 18 years old with diagnosed HIV and at least 6 months of ongoing treatment with dolutegravir/ doravirin/lamivudine will be included. Patients must have a plasma viral load (HIV-RNA) < 50 copies/ml at inclusion. For women of childbearing potential: Negative pregnancy test and willingness to use contraceptive (consistent with local regulations) during study period
Exclusion Criteria:
- Patients will be excluded in case of pre-existing viral resistance mutations to lamivudine, dolutegravir, tenofovir or doravirine the presence of hepatitis B antigen (HBsAg) or HBV DNA, cancer within past 5 years, pregnancy or breastfeeding. Any case of diabetes, cardiovascular disease or other chronic illness must be considered stable as assessed by the treating physician.
Sites / Locations
- Department of Infectious Diseases, Aalborg University Hospital
- Department of Infectious Diseases, Aarhus University Hospital
- Department of Infectious Diseases, Rigshospitalet
- Department of Infectious Diseases, Hvidovre University HospitalRecruiting
- Department of Infectious Diseases, Odense University Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
No Intervention
Experimental
Experimental
Arm Label
Dolutegravir/tenofovir disproxil/lamivudine
dolutegravir/lamivudine
doravirine/tenofovir disproxil/lamivudine
Arm Description
Continue dolutegravir 50 mg, tenofovir disproxil 245 mg, ,and lamivudine 300 mg once daily for 48 weeks.
dolutegravir 50 mg/lamivudine 300 mg once daily for 48 weeks
100 mg doravirin, 245 mg tenofovirdisoproxil and 300 mg lamivudine once daily for 48 weeks.
Outcomes
Primary Outcome Measures
Body weight
Primary outcome is a change in body weight of more than 2 kg from
Secondary Outcome Measures
Virological control
Plasma HIV-RNA <50 copies/ml
Self-rated health
Changes in 12-item Short Form Health Survey (SF-12). Scores from 0 (worse) to 100 (best).
Insulin resistance
Impaired insulin resistance and/or β-cell function determined by changes in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)
Diabetic profile
Changes in HbA1c
Cholesterol profile
Changes in cholesterol total, HDL, LDL, VLDL
Fat distribution
Changes in Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) determined by thoracic and upper abdominal CT-scan.
Hepatic elasticity
Changes in hepativ elasticity determined by liver elastography (Fibro-scan)
Hepatic fat infiltration
Changes in hepatic fat infiltration determined by liver elastography (Fibro-scan) and upper abdominal CT-scan
Body composition/perfiferal and central fat distribution
Changes in body fat distribtuion determined bu Dual Energy X-ray Absorbtiometry (DEXA)
Estimated Glomerular Filtration Rate (eGFR) (creatinine)
Changes in eGFR estimated by plasma creatinine
eGFR (cystatin)
Changes in estimated by plasma cystatin
Urea
Changes in plasma urea
Urine RBP/creatinine ratio
Changes in Urine RBP/creatinine ratio determined by spot urine Retinol Binding Protein (RBP) and creatinine analysis
Urine Beta-2-Microglobulin(B2M)/creatinine ratio
Changes in B2M/creatinine ratio determined by spot urine B2M and creatinine
Urine albumin/creatinine ratio
Changes in Urine albumin/creatinine ratio determined by spot urine albumine and creatinine analysis
Urine protein/creatinine ratio
Changes in urine protein/creatinine ratio determined by spot urine protein and creatinine analysis
Urine phosphate
Changes in spot urine phosphate
Bone mass density (BMD)
Changes in BMD assessed by DEXA
Bone-specific alkaline phosphate
Changes in plasma Bone-specific alkaline phosphate
Procollagen type 1 N-pro-peptide
Changes in procollagen type 1 N-pro-peptide
Type 1 collagen cross-linked C-telopeptide
Changes in plasma Type 1 collagen cross-linked C-telopeptide
Osteocalcin
Changes in plasma osteocalcin
Fasting ionized calcium
Changes in plasma fasting ionized calcium
25(OH)vitamin D vitamin D 25(OH)vitamin D
Changes in plasma 25(OH)vitamin D
Parathyroid hormone (PTH) vitamin D 25(OH)vitamin D
Changes in plasma parathyroid hormone (PTH)
Inflammation
High-sensitive C-reactive protein
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04903847
Brief Title
Changes in Weight, Body Composition and Metabolic Parameters After Discontinuing Dolutegravir or Tenofovir Disproxil
Acronym
AVERTAS-2
Official Title
Changes in Weight After Switch to Dolutegravir/Lamivudine or Doravirine/Tenofovir/Lamivudine Compared to Continued Treatment With Dolutegravir/Tenofovir/Lamivudine for Virologically Suppressed HIV Infection. AVERTAS-2
Study Type
Interventional
2. Study Status
Record Verification Date
May 2021
Overall Recruitment Status
Unknown status
Study Start Date
February 2, 2021 (Actual)
Primary Completion Date
February 2, 2023 (Anticipated)
Study Completion Date
February 2, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Thomas Benfield
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Randomized controlled parallel open-label study in persons living with HIV. The aim is to study weight changes in patients switching from a dolutegravir and tenofovir disoproxil containing regimen to either a dolutegravir or tenofovir disoproxil free regimen.
Detailed Description
Randomized controlled parallel open-label study in persons living with HIV and at least 6 month of treatment with dolutegravir/abacavir/lamivudine prior to inclusion.
Participants (n=126) are randomized to continue 3 drug-regimen dolutegravir/tenofovir disoproxil/lamivudine (control) or switch to two-drug regimen with dolutegravir/lamivudine (intervention 1) or to three-drug regimen with doravirine/tenofovir disoproxil/lamivudine. 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 virus persistent viral suppression, changes in body composition and metabolism, changes in bone metabolisme and renal function, changes in liver elasticity and fat infiltration.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hiv, HIV Infections, HIV Lipodystrophy, Osteoporosis, Renal Insufficiency, Weight Gain, Obesity
Keywords
HIV, antiretroviral therapy, antiretroviral therapy adverse events, weight gain, body composition, fat distribution
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Randomized controlled open-label superiority trial
Masking
None (Open Label)
Allocation
Randomized
Enrollment
126 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Dolutegravir/tenofovir disproxil/lamivudine
Arm Type
No Intervention
Arm Description
Continue dolutegravir 50 mg, tenofovir disproxil 245 mg, ,and lamivudine 300 mg once daily for 48 weeks.
Arm Title
dolutegravir/lamivudine
Arm Type
Experimental
Arm Description
dolutegravir 50 mg/lamivudine 300 mg once daily for 48 weeks
Arm Title
doravirine/tenofovir disproxil/lamivudine
Arm Type
Experimental
Arm Description
100 mg doravirin, 245 mg tenofovirdisoproxil and 300 mg lamivudine once daily for 48 weeks.
Intervention Type
Drug
Intervention Name(s)
Dolutegravir/Lamivudine 50 MG-300 MG Oral Tablet [DOVATO]
Other Intervention Name(s)
Dovato
Intervention Description
Two-drug therapy
Intervention Type
Drug
Intervention Name(s)
Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate 100 MG-300 MG-300 MG Oral Tablet [DELSTRIGO]
Other Intervention Name(s)
Delstrigo
Intervention Description
Three-drug therapy
Primary Outcome Measure Information:
Title
Body weight
Description
Primary outcome is a change in body weight of more than 2 kg from
Time Frame
48 Weeks
Secondary Outcome Measure Information:
Title
Virological control
Description
Plasma HIV-RNA <50 copies/ml
Time Frame
48 weeks
Title
Self-rated health
Description
Changes in 12-item Short Form Health Survey (SF-12). Scores from 0 (worse) to 100 (best).
Time Frame
48 weeks
Title
Insulin resistance
Description
Impaired insulin resistance and/or β-cell function determined by changes in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)
Time Frame
48 weeks
Title
Diabetic profile
Description
Changes in HbA1c
Time Frame
48 weeks
Title
Cholesterol profile
Description
Changes in cholesterol total, HDL, LDL, VLDL
Time Frame
48 weeks
Title
Fat distribution
Description
Changes in Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) determined by thoracic and upper abdominal CT-scan.
Time Frame
48 weeks
Title
Hepatic elasticity
Description
Changes in hepativ elasticity determined by liver elastography (Fibro-scan)
Time Frame
48 weeks
Title
Hepatic fat infiltration
Description
Changes in hepatic fat infiltration determined by liver elastography (Fibro-scan) and upper abdominal CT-scan
Time Frame
48 weeks
Title
Body composition/perfiferal and central fat distribution
Description
Changes in body fat distribtuion determined bu Dual Energy X-ray Absorbtiometry (DEXA)
Time Frame
48 weeks
Title
Estimated Glomerular Filtration Rate (eGFR) (creatinine)
Description
Changes in eGFR estimated by plasma creatinine
Time Frame
48 weeks
Title
eGFR (cystatin)
Description
Changes in estimated by plasma cystatin
Time Frame
48 weeks
Title
Urea
Description
Changes in plasma urea
Time Frame
48 weeks
Title
Urine RBP/creatinine ratio
Description
Changes in Urine RBP/creatinine ratio determined by spot urine Retinol Binding Protein (RBP) and creatinine analysis
Time Frame
48 weeks
Title
Urine Beta-2-Microglobulin(B2M)/creatinine ratio
Description
Changes in B2M/creatinine ratio determined by spot urine B2M and creatinine
Time Frame
48 weeks
Title
Urine albumin/creatinine ratio
Description
Changes in Urine albumin/creatinine ratio determined by spot urine albumine and creatinine analysis
Time Frame
48 weeks
Title
Urine protein/creatinine ratio
Description
Changes in urine protein/creatinine ratio determined by spot urine protein and creatinine analysis
Time Frame
48 weeks
Title
Urine phosphate
Description
Changes in spot urine phosphate
Time Frame
48 weeks
Title
Bone mass density (BMD)
Description
Changes in BMD assessed by DEXA
Time Frame
48 weeks
Title
Bone-specific alkaline phosphate
Description
Changes in plasma Bone-specific alkaline phosphate
Time Frame
48 weeks
Title
Procollagen type 1 N-pro-peptide
Description
Changes in procollagen type 1 N-pro-peptide
Time Frame
48 weeks
Title
Type 1 collagen cross-linked C-telopeptide
Description
Changes in plasma Type 1 collagen cross-linked C-telopeptide
Time Frame
48 weeks
Title
Osteocalcin
Description
Changes in plasma osteocalcin
Time Frame
48 weeks
Title
Fasting ionized calcium
Description
Changes in plasma fasting ionized calcium
Time Frame
48 weeks
Title
25(OH)vitamin D vitamin D 25(OH)vitamin D
Description
Changes in plasma 25(OH)vitamin D
Time Frame
48 weeks
Title
Parathyroid hormone (PTH) vitamin D 25(OH)vitamin D
Description
Changes in plasma parathyroid hormone (PTH)
Time Frame
48 weeks
Title
Inflammation
Description
High-sensitive C-reactive protein
Time Frame
48 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Individuals ≥ 18 years old with diagnosed HIV and at least 6 months of ongoing treatment with dolutegravir/ doravirin/lamivudine will be included. Patients must have a plasma viral load (HIV-RNA) < 50 copies/ml at inclusion. For women of childbearing potential: Negative pregnancy test and willingness to use contraceptive (consistent with local regulations) during study period
Exclusion Criteria:
Patients will be excluded in case of pre-existing viral resistance mutations to lamivudine, dolutegravir, tenofovir or doravirine the presence of hepatitis B antigen (HBsAg) or HBV DNA, cancer within past 5 years, pregnancy or breastfeeding. Any case of diabetes, cardiovascular disease or other chronic illness must be considered stable as assessed by the treating physician.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Karen BH Pedersen, MD
Phone
+4521623027
Email
karen.brorup.heje.pedersen@regionh.dk
First Name & Middle Initial & Last Name or Official Title & Degree
Thomas Benfield, MD
Email
thomas.lars.benfield@regionh.dk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas Benfield, MD
Organizational Affiliation
Center of Research and Disruption of Infectious Diseases
Official's Role
Study Director
Facility Information:
Facility Name
Department of Infectious Diseases, Aalborg University Hospital
City
Aalborg
ZIP/Postal Code
9000
Country
Denmark
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Henrik Nielsen, MD, DMSc
Facility Name
Department of Infectious Diseases, Aarhus University Hospital
City
Aarhus
ZIP/Postal Code
8200
Country
Denmark
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alex L Laursen, MD, PhD
Facility Name
Department of Infectious Diseases, Rigshospitalet
City
Copenhagen
ZIP/Postal Code
2100
Country
Denmark
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jan Gerstoft, MD, DMSc
Facility Name
Department of Infectious Diseases, Hvidovre University Hospital
City
Hvidovre
ZIP/Postal Code
2650
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Karen BH Pedersen, MD
Phone
+4521623027
Email
karen.brorup.heje.pedersen@regionh.dk
Facility Name
Department of Infectious Diseases, Odense University Hospital
City
Odense
ZIP/Postal Code
5000
Country
Denmark
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Isik S Johansen, MD, DMSc
12. IPD Sharing Statement
Citations:
PubMed Identifier
20345879
Citation
Belloso WH, Orellana LC, Grinsztejn B, Madero JS, La Rosa A, Veloso VG, Sanchez J, Ismerio Moreira R, Crabtree-Ramirez B, Garcia Messina O, Lasala MB, Peinado J, Losso MH. Analysis of serious non-AIDS events among HIV-infected adults at Latin American sites. HIV Med. 2010 Oct 1;11(9):554-64. doi: 10.1111/j.1468-1293.2010.00824.x. Epub 2010 Mar 21.
Results Reference
background
PubMed Identifier
25042234
Citation
Smith CJ, Ryom L, Weber R, Morlat P, Pradier C, Reiss P, Kowalska JD, de Wit S, Law M, el Sadr W, Kirk O, Friis-Moller N, Monforte Ad, Phillips AN, Sabin CA, Lundgren JD; D:A:D Study Group. Trends in underlying causes of death in people with HIV from 1999 to 2011 (D:A:D): a multicohort collaboration. Lancet. 2014 Jul 19;384(9939):241-8. doi: 10.1016/S0140-6736(14)60604-8.
Results Reference
background
PubMed Identifier
15911733
Citation
Brown TT, Cole SR, Li X, Kingsley LA, Palella FJ, Riddler SA, Visscher BR, Margolick JB, Dobs AS. Antiretroviral therapy and the prevalence and incidence of diabetes mellitus in the multicenter AIDS cohort study. Arch Intern Med. 2005 May 23;165(10):1179-84. doi: 10.1001/archinte.165.10.1179. Erratum In: Arch Intern Med. 2005 Nov 28;165(21):2541.
Results Reference
background
PubMed Identifier
26352511
Citation
Koethe JR, Jenkins CA, Lau B, Shepherd BE, Justice AC, Tate JP, Buchacz K, Napravnik S, Mayor AM, Horberg MA, Blashill AJ, Willig A, Wester CW, Silverberg MJ, Gill J, Thorne JE, Klein M, Eron JJ, Kitahata MM, Sterling TR, Moore RD; North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). Rising Obesity Prevalence and Weight Gain Among Adults Starting Antiretroviral Therapy in the United States and Canada. AIDS Res Hum Retroviruses. 2016 Jan;32(1):50-8. doi: 10.1089/aid.2015.0147. Epub 2015 Sep 9.
Results Reference
background
PubMed Identifier
29722811
Citation
Bakal DR, Coelho LE, Luz PM, Clark JL, De Boni RB, Cardoso SW, Veloso VG, Lake JE, Grinsztejn B. Obesity following ART initiation is common and influenced by both traditional and HIV-/ART-specific risk factors. J Antimicrob Chemother. 2018 Aug 1;73(8):2177-2185. doi: 10.1093/jac/dky145.
Results Reference
background
PubMed Identifier
30800425
Citation
Hill A, Waters L, Pozniak A. Are new antiretroviral treatments increasing the risks of clinical obesity? J Virus Erad. 2019 Jan 1;5(1):41-43.
Results Reference
background
PubMed Identifier
31606734
Citation
Sax PE, Erlandson KM, Lake JE, Mccomsey GA, Orkin C, Esser S, Brown TT, Rockstroh JK, Wei X, Carter CC, Zhong L, Brainard DM, Melbourne K, Das M, Stellbrink HJ, Post FA, Waters L, Koethe JR. Weight Gain Following Initiation of Antiretroviral Therapy: Risk Factors in Randomized Comparative Clinical Trials. Clin Infect Dis. 2020 Sep 12;71(6):1379-1389. doi: 10.1093/cid/ciz999.
Results Reference
background
PubMed Identifier
31567162
Citation
Burns JE, Stirrup OT, Dunn D, Runcie-Unger I, Milinkovic A, Candfield S, Lukha H, Severn A, Waters L, Edwards S, Gilson R, Pett SL. No overall change in the rate of weight gain after switching to an integrase-inhibitor in virologically suppressed adults with HIV. AIDS. 2020 Jan 1;34(1):109-114. doi: 10.1097/QAD.0000000000002379.
Results Reference
background
PubMed Identifier
31714355
Citation
Vizcarra P, Vivancos MJ, Perez-Elias MJ, Moreno A, Casado JL. Weight gain in people living with HIV switched to dual therapy: changes in body fat mass. AIDS. 2020 Jan 1;34(1):155-157. doi: 10.1097/QAD.0000000000002421.
Results Reference
background
PubMed Identifier
31331365
Citation
Nartey ET, Tetteh RA, Yankey BA, Mantel-Teeuwisse AK, Leufkens HGM, Dodoo ANO, Lartey M. Tenofovir-associated renal toxicity in a cohort of HIV infected patients in Ghana. BMC Res Notes. 2019 Jul 22;12(1):445. doi: 10.1186/s13104-019-4454-2.
Results Reference
background
PubMed Identifier
25259702
Citation
Nishijima T, Kawasaki Y, Tanaka N, Mizushima D, Aoki T, Watanabe K, Kinai E, Honda H, Yazaki H, Tanuma J, Tsukada K, Teruya K, Kikuchi Y, Gatanaga H, Oka S. Long-term exposure to tenofovir continuously decrease renal function in HIV-1-infected patients with low body weight: results from 10 years of follow-up. AIDS. 2014 Aug 24;28(13):1903-10. doi: 10.1097/QAD.0000000000000347.
Results Reference
background
PubMed Identifier
26919733
Citation
Casado JL, Santiuste C, Vazquez M, Banon S, Rosillo M, Gomez A, Perez-Elias MJ, Caballero C, Rey JM, Moreno S. Bone mineral density decline according to renal tubular dysfunction and phosphaturia in tenofovir-exposed HIV-infected patients. AIDS. 2016 Jun 1;30(9):1423-31. doi: 10.1097/QAD.0000000000001067.
Results Reference
background
PubMed Identifier
28369419
Citation
Gupta SK, Yeh E, Kitch DW, Brown TT, Venuto CS, Morse GD, Ha B, Melbourne K, McComsey GA. Bone mineral density reductions after tenofovir disoproxil fumarate initiation and changes in phosphaturia: a secondary analysis of ACTG A5224s. J Antimicrob Chemother. 2017 Jul 1;72(7):2042-2048. doi: 10.1093/jac/dkx076.
Results Reference
background
PubMed Identifier
18845956
Citation
Jacobson DL, Spiegelman D, Knox TK, Wilson IB. Evolution and predictors of change in total bone mineral density over time in HIV-infected men and women in the nutrition for healthy living study. J Acquir Immune Defic Syndr. 2008 Nov 1;49(3):298-308. doi: 10.1097/QAI.0b013e3181893e8e.
Results Reference
background
Learn more about this trial
Changes in Weight, Body Composition and Metabolic Parameters After Discontinuing Dolutegravir or Tenofovir Disproxil
We'll reach out to this number within 24 hrs