Body Composition Sub-study of the D2EFT Trial

This is a non-randomised, controlled, parallel group, sub-study of D2EFT (NCT03017872), a randomised, open-label study in approximately 1,000 HIV-infected adults failing first-line antiretroviral therapy (ART) in low-middle income countries. The sub-study will be offered to all D2EFT sites with access to DXA technology for whole-body composition analysis. Sites will offer the sub-study to consecutive clinic patients. Patients must be approached for participation and provide informed written consent prior to randomisation into D2EFT. This study will recruit approximately 300 patients. Allocation to one of three ART treatment regimens will follow the result of D2EFT randomisation. The study will investigate the role of contemporary ART on body composition and metabolic parameters by comparing over 96 weeks the effects of the D2EFT ART regimens. The primary endpoint will be assessed at week 48.

Study Overview

• Status: Active, not recruiting
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Darunavir (DRV) 800 milligram (MG) Oral Tablet; Drug: Ritonavir 100 MG Oral Tablet; Drug: N(t)RTIs; Drug: Dolutegravir 50 MG Oral Tablet; Drug: TDF 300 MG Oral Tablet; Drug: 3TC 300 MG Oral Tablet; Drug: FTC 200 MG Oral Cap

Detailed Description

Consenting participants will be randomised within the main D2EFT protocol to receive either ritonavir-boosted darunavir plus two nucleosides or dolutegravir plus two predetermined nucleosides (lamivudine or emtricitabine) or ritonavir-boosted darunavir plus dolutegravir. Enrolment into the sub-study is voluntary and not a requirement for enrolment into D2EFT. Parameters relevant to this study including demographics, arm of randomised ART, smoking status, body habitus and fasting lipid parameters and resting blood pressure at required time points will be collected as part of the main D2EFT study. Sub-study specific assessments performed at baseline and at weeks 48 and 96 include clinical and laboratory assessments, sample collection and dual-energy X-ray absorptiometry (DXA)-assessed whole-body composition. Consenting participants will have blood for storage collected at weeks 0, 48 and 96. The specimens will be used for future studies into treatment of HIV infection and immunity.

• Study Type: Interventional
• Enrollment (Actual): 155
• Phase: Phase 4

Contacts and Locations

Study Locations

• India
  • Chennai, India, 600113
    • Chennai Antiviral Research aznd Treatment (CART) Clinical Research Site
• Malaysia
  • Kuala Lumpur, Malaysia
    • Univerity of Malaya Medical Centre
• South Africa
  • Cape Town, South Africa, 9725
    • Desmond Tutu HIV Foundation
  • Johannesburg
    • Soweto, Johannesburg, South Africa, 2013
      • Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital
    • Westdene, Johannesburg, South Africa
      • Clinical HIV Research Unit, Helen Joseph Hospital
• Thailand
  • Bangkok, Thailand, 10330
    • The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Thai Red Cross Research Centre
• Zimbabwe
  • Harare, Zimbabwe, 263
    • University of Zimbabwe Clinical Research Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Fulfil the criteria for D2EFT randomisation
• Able to undergo DXA whole-body scanning
• Provide informed written consent for the D2EFT Body Composition Sub-study

Exclusion Criteria:

• Unwilling to comply with the study requirements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard of care; darunavir 800 mg oral tablet + ritonavir 100 mg oral tablet + (N(t)RTIs) po qd	Drug: Darunavir (DRV) 800 milligram (MG) Oral Tablet; 800 milligrams (mg) orally once daily for 96 weeks; Other Names: Prezista; Drug: Ritonavir 100 MG Oral Tablet; 100 mg orally once daily for 96 weeks; Other Names: Norvir, RTV; Drug: N(t)RTIs; Choice of N(t)RTIs determined by clinician guided by either genotypic resistance testing or use of a protocol-specified algorithm for N(t)RTI selection; Other Names: Nucleoside/nucleotide reverse transcriptase inhibitors [N(t)RTIs]
Experimental: Dolutegravir + tenofovir (TDF) + either lamivudine (3TC) or emtricitabine (FTC); dolutegravir 50 mg oral tablet + TDF 300 mg oral tablet + either 3TC 300 mg oral tablet or FTC 200 mg oral capsule po qd	Drug: Dolutegravir 50 MG Oral Tablet; 50 mg orally once daily for 96 weeks; Other Names: Tivicay, DTG; Drug: TDF 300 MG Oral Tablet; 300 mg orally once daily for 96 weeks; Other Names: tenofovir disoproxil fumarate, Viread; Drug: 3TC 300 MG Oral Tablet; 300 mg orally once daily for 96 weeks. Choice of 3TC or FTC will be determined by clinician; Other Names: lamivudine; Drug: FTC 200 MG Oral Cap; 200 mg orally once daily for 96 weeks. Choice of emtricitabine or lamivudine will be determined by clinician; Other Names: Emtriva, emtricitabine
Experimental: Dolutegravir + darunavir; dolutegravir 50 mg oral tablet + darunavir 800 mg oral tablet + ritonavir 100 mg oral tablet po qd	Drug: Darunavir (DRV) 800 milligram (MG) Oral Tablet; 800 milligrams (mg) orally once daily for 96 weeks; Other Names: Prezista; Drug: Ritonavir 100 MG Oral Tablet; 100 mg orally once daily for 96 weeks; Other Names: Norvir, RTV; Drug: Dolutegravir 50 MG Oral Tablet; 50 mg orally once daily for 96 weeks; Other Names: Tivicay, DTG

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean/median between-group change in waist-to-hip ratio	umbilical waist and hip measures	at 48 weeks
Mean/median between-group change in total-to-HDL cholesterol ratio	total and HDL cholesterol plasma concentrations	at 48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean/median between-group change in total-to-HDL cholesterol ratio	total and HDL cholesterol plasma concentrations	at 96 weeks
Mean/median between-group change in waist-to-hip ratio	umbilical waist and hip measures	at 96 weeks
Mean/median between-group change in body weight	body weight measurement	at week 48 and 96
Mean/median between-group change in maximum umbilical and hip measures	umbilical waist and hip measures	at week 48 and 96
Mean/median between-group change in fasting lipid parameters	total, HDL, and LDL cholesterol and triglyceride plasma concentrations	at weeks 48 and 96
Mean/median between-group change in fasting glycaemic parameters	glucose, insulin, HbA1c concentrations	at weeks 48 and 96
Mean/median between-group absolute change in limb fat assessed by DXA	absolute change from baseline in limb fat	week 48 and 96
Mean/median between-group percentage change in limb fat assessed by DXA	percentage change from baseline in limb fat	week 48 and 96
Mean/median between-group changes in regional body fat assessed by DXA	regional = limb fat and truncal fat	week 48 and 96
Mean/median between-group changes in total body fat and lean tissue assessed by DXA	total body fat and total lean tissue	week 48 and 96
Mean/median between-group changes in bone mineral content assessed by DXA	total bone mineral content	week 48 and 96
Mean/median between-group change in Body Image questionnaire scores	NIAID Adult AIDS Clinical Trials Group Baseline and Follow-up questionnaires	weeks 48 and 96
Proportion with Metabolic Syndrome	baseline prevalence and incidence at weeks 48 and 96	week 0, and week 48 and 96

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean/median between-group change in serum biomarker concentrations	biomarkers to be determined	weeks 48 and 96

Collaborators and Investigators

• Sponsor: Kirby Institute
• Investigators: Principal Investigator: Gail Matthews, MBBCh, The Kirby Institute, UNSW Sydney

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2019
• Primary Completion (Estimated): January 15, 2024
• Study Completion (Estimated): January 15, 2024

Study Registration Dates

• First Submitted: July 2, 2018
• First Submitted That Met QC Criteria: September 16, 2018
• First Posted (Actual): September 18, 2018

Study Record Updates

• Last Update Posted (Actual): July 25, 2023
• Last Update Submitted That Met QC Criteria: July 24, 2023
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Urogenital Diseases; Genital Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Integrase Inhibitors; Integrase Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Tenofovir; Emtricitabine; Ritonavir; Lamivudine; Reverse Transcriptase Inhibitors; Darunavir; Dolutegravir
• Other Study ID Numbers: D2EFT BodyComp

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No