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

NCT04903847 | Unknown Phase 4 DMC

• 1 other identifier: H-20012194
• Study Type: interventional
• Target: 126
• Locations: 1 country
• Sites: 5

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Body weight

  Primary outcome is a change in body weight of more than 2 kg from

  48 Weeks

Secondary Outcomes (26)

• Virological control

  48 weeks

• Self-rated health

  48 weeks

• Insulin resistance

  48 weeks

• Diabetic profile

  48 weeks

• Cholesterol profile

  48 weeks

Study Arms (3)

Dolutegravir/tenofovir disproxil/lamivudine

NO INTERVENTION

Continue dolutegravir 50 mg, tenofovir disproxil 245 mg, ,and lamivudine 300 mg once daily for 48 weeks.

dolutegravir/lamivudine

EXPERIMENTAL

dolutegravir 50 mg/lamivudine 300 mg once daily for 48 weeks

Drug: Dolutegravir/Lamivudine 50 MG-300 MG Oral Tablet [DOVATO]

doravirine/tenofovir disproxil/lamivudine

EXPERIMENTAL

100 mg doravirin, 245 mg tenofovirdisoproxil and 300 mg lamivudine once daily for 48 weeks.

Drug: Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate 100 MG-300 MG-300 MG Oral Tablet [DELSTRIGO]

Interventions

Dolutegravir/Lamivudine 50 MG-300 MG Oral Tablet [DOVATO] DRUG

Two-drug therapy

Also known as: Dovato

dolutegravir/lamivudine

Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate 100 MG-300 MG-300 MG Oral Tablet [DELSTRIGO] DRUG

Three-drug therapy

Also known as: Delstrigo

doravirine/tenofovir disproxil/lamivudine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Thomas Benfield: lead

Study Sites (5)

Department of Infectious Diseases, Aalborg University Hospital

Aalborg, 9000, Denmark

NOT YET RECRUITING

Department of Infectious Diseases, Aarhus University Hospital

Aarhus, 8200, Denmark

NOT YET RECRUITING

Department of Infectious Diseases, Rigshospitalet

Copenhagen, 2100, Denmark

NOT YET RECRUITING

Department of Infectious Diseases, Hvidovre University Hospital

Hvidovre, 2650, Denmark

RECRUITING

Department of Infectious Diseases, Odense University Hospital

Odense, 5000, Denmark

NOT YET RECRUITING

Related Publications (14)

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  PMID: 25042234 BACKGROUND

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  PMID: 15911733 BACKGROUND

• 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.

  PMID: 26352511 BACKGROUND

• 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.

  PMID: 29722811 BACKGROUND

• 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. doi: 10.1016/S2055-6640(20)30277-6.

  PMID: 30800425 BACKGROUND

• 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.

  PMID: 31606734 BACKGROUND

• 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.

  PMID: 31567162 BACKGROUND

• 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.

  PMID: 31714355 BACKGROUND

• 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.

  PMID: 31331365 BACKGROUND

• 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.

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• 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.

  PMID: 28369419 BACKGROUND

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  PMID: 18845956 BACKGROUND

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; HIV Infections; Osteoporosis; Renal Insufficiency; Weight Gain; Obesity

Interventions

dolutegravir; Lamivudine; doravirine; Tenofovir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Male Urogenital Diseases; Body Weight Changes; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Overweight; Overnutrition; Nutrition Disorders

Intervention Hierarchy (Ancestors)

Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Thomas Benfield, MD

  Center of Research and Disruption of Infectious Diseases

  STUDY DIRECTOR

Central Study Contacts

Karen BH Pedersen, MD

CONTACT

+4521623027; karen.brorup.heje.pedersen@regionh.dk

Thomas Benfield, MD

CONTACT

thomas.lars.benfield@regionh.dk

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, professor, dr.med.

Model Details: Randomized controlled open-label superiority trial

Study Record Dates

• First Submitted: October 9, 2020
• First Posted: May 27, 2021
• Study Start: February 2, 2021
• Primary Completion: February 2, 2023
• Study Completion: February 2, 2023
• Last Updated: May 27, 2021

Record last verified: 2021-05

Locations

DK (5)