Changes in Weight, Body Composition and Metabolic Parameters After Discontinuing Dolutegravir or Tenofovir Disproxil

Obesity Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04903847
• Other study ID #: H-20012194
• Status: Recruiting
• Phase: Phase 4
• Start date: February 2, 2021
• Est. completion date: February 2, 2023

Study information

• Verified date: May 2021
• Source: Hvidovre University Hospital
• Contact: Karen BH Pedersen, MD
• Phone: +4521623027
• Email: karen.brorup.heje.pedersen[@]regionh.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 126
• Est. completion date: February 2, 2023
• Est. primary completion date: February 2, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• Body Weight
• Hiv
• HIV Infections
• HIV Lipodystrophy
• Infection
• Lipodystrophy
• Obesity
• Osteoporosis
• Renal Insufficiency
• Weight Gain

Intervention

Drug:
• Dolutegravir/Lamivudine 50 MG-300 MG Oral Tablet [DOVATO]
Two-drug therapy
• Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate 100 MG-300 MG-300 MG Oral Tablet [DELSTRIGO]
Three-drug therapy

Locations

Country	Name	City	State
Denmark	Department of Infectious Diseases, Aalborg University Hospital	Aalborg
Denmark	Department of Infectious Diseases, Aarhus University Hospital	Aarhus
Denmark	Department of Infectious Diseases, Rigshospitalet	Copenhagen
Denmark	Department of Infectious Diseases, Hvidovre University Hospital	Hvidovre
Denmark	Department of Infectious Diseases, Odense University Hospital	Odense

Sponsors (1)

Lead Sponsor	Collaborator
Thomas Benfield

Country where clinical trial is conducted

Denmark, 

References & Publications (14)

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. — View 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. — View 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. Erratum in: Arch Intern Med. 2005 Nov 28;165(21):2541. — View 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. — View Citation

Casado JL, Santiuste C, Vazquez M, Bañón S, Rosillo M, Gomez A, Perez-Elías 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Vizcarra P, Vivancos MJ, Pérez-Elías 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. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Body weight	Primary outcome is a change in body weight of more than 2 kg from	48 Weeks
Secondary	Virological control	Plasma HIV-RNA <50 copies/ml	48 weeks
Secondary	Self-rated health	Changes in 12-item Short Form Health Survey (SF-12). Scores from 0 (worse) to 100 (best).	48 weeks
Secondary	Insulin resistance	Impaired insulin resistance and/or ß-cell function determined by changes in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)	48 weeks
Secondary	Diabetic profile	Changes in HbA1c	48 weeks
Secondary	Cholesterol profile	Changes in cholesterol total, HDL, LDL, VLDL	48 weeks
Secondary	Fat distribution	Changes in Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) determined by thoracic and upper abdominal CT-scan.	48 weeks
Secondary	Hepatic elasticity	Changes in hepativ elasticity determined by liver elastography (Fibro-scan)	48 weeks
Secondary	Hepatic fat infiltration	Changes in hepatic fat infiltration determined by liver elastography (Fibro-scan) and upper abdominal CT-scan	48 weeks
Secondary	Body composition/perfiferal and central fat distribution	Changes in body fat distribtuion determined bu Dual Energy X-ray Absorbtiometry (DEXA)	48 weeks
Secondary	Estimated Glomerular Filtration Rate (eGFR) (creatinine)	Changes in eGFR estimated by plasma creatinine	48 weeks
Secondary	eGFR (cystatin)	Changes in estimated by plasma cystatin	48 weeks
Secondary	Urea	Changes in plasma urea	48 weeks
Secondary	Urine RBP/creatinine ratio	Changes in Urine RBP/creatinine ratio determined by spot urine Retinol Binding Protein (RBP) and creatinine analysis	48 weeks
Secondary	Urine Beta-2-Microglobulin(B2M)/creatinine ratio	Changes in B2M/creatinine ratio determined by spot urine B2M and creatinine	48 weeks
Secondary	Urine albumin/creatinine ratio	Changes in Urine albumin/creatinine ratio determined by spot urine albumine and creatinine analysis	48 weeks
Secondary	Urine protein/creatinine ratio	Changes in urine protein/creatinine ratio determined by spot urine protein and creatinine analysis	48 weeks
Secondary	Urine phosphate	Changes in spot urine phosphate	48 weeks
Secondary	Bone mass density (BMD)	Changes in BMD assessed by DEXA	48 weeks
Secondary	Bone-specific alkaline phosphate	Changes in plasma Bone-specific alkaline phosphate	48 weeks
Secondary	Procollagen type 1 N-pro-peptide	Changes in procollagen type 1 N-pro-peptide	48 weeks
Secondary	Type 1 collagen cross-linked C-telopeptide	Changes in plasma Type 1 collagen cross-linked C-telopeptide	48 weeks
Secondary	Osteocalcin	Changes in plasma osteocalcin	48 weeks
Secondary	Fasting ionized calcium	Changes in plasma fasting ionized calcium	48 weeks
Secondary	25(OH)vitamin D vitamin D 25(OH)vitamin D	Changes in plasma 25(OH)vitamin D	48 weeks
Secondary	Parathyroid hormone (PTH) vitamin D 25(OH)vitamin D	Changes in plasma parathyroid hormone (PTH)	48 weeks
Secondary	Inflammation	High-sensitive C-reactive protein	48 weeks