Body Composition Sub-study of the D2EFT Trial

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Body Composition Sub-study of the D2EFT Trial

Conditions
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HIV Infections

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 |