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Body Composition Sub-study of the D2EFT Trial

Phase 4
Completed
Conditions
HIV Infections
Interventions
Registration Number
NCT03675815
Lead Sponsor
Kirby Institute
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
155
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Dolutegravir + tenofovir (TDF) + either lamivudine (3TC) or emtricitabine (FTC)TDF 300 MG Oral Tabletdolutegravir 50 mg oral tablet + TDF 300 mg oral tablet + either 3TC 300 mg oral tablet or FTC 200 mg oral capsule po qd
Standard of careRitonavir 100 MG Oral Tabletdarunavir 800 mg oral tablet + ritonavir 100 mg oral tablet + (N(t)RTIs) po qd
Standard of careN(t)RTIsdarunavir 800 mg oral tablet + ritonavir 100 mg oral tablet + (N(t)RTIs) po qd
Dolutegravir + tenofovir (TDF) + either lamivudine (3TC) or emtricitabine (FTC)3TC 300 MG Oral Tabletdolutegravir 50 mg oral tablet + TDF 300 mg oral tablet + either 3TC 300 mg oral tablet or FTC 200 mg oral capsule po qd
Dolutegravir + tenofovir (TDF) + either lamivudine (3TC) or emtricitabine (FTC)FTC 200 MG Oral Capdolutegravir 50 mg oral tablet + TDF 300 mg oral tablet + either 3TC 300 mg oral tablet or FTC 200 mg oral capsule po qd
Dolutegravir + darunavirDarunavir (DRV) 800 milligram (MG) Oral Tabletdolutegravir 50 mg oral tablet + darunavir 800 mg oral tablet + ritonavir 100 mg oral tablet po qd
Dolutegravir + darunavirRitonavir 100 MG Oral Tabletdolutegravir 50 mg oral tablet + darunavir 800 mg oral tablet + ritonavir 100 mg oral tablet po qd
Dolutegravir + darunavirDolutegravir 50 MG Oral Tabletdolutegravir 50 mg oral tablet + darunavir 800 mg oral tablet + ritonavir 100 mg oral tablet po qd
Standard of careDarunavir (DRV) 800 milligram (MG) Oral Tabletdarunavir 800 mg oral tablet + ritonavir 100 mg oral tablet + (N(t)RTIs) po qd
Dolutegravir + tenofovir (TDF) + either lamivudine (3TC) or emtricitabine (FTC)Dolutegravir 50 MG Oral Tabletdolutegravir 50 mg oral tablet + TDF 300 mg oral tablet + either 3TC 300 mg oral tablet or FTC 200 mg oral capsule po qd
Primary Outcome Measures
NameTimeMethod
Mean/median between-group change in waist-to-hip ratioat 48 weeks

umbilical waist and hip measures

Mean/median between-group change in total-to-HDL cholesterol ratioat 48 weeks

total and HDL cholesterol plasma concentrations

Secondary Outcome Measures
NameTimeMethod
Mean/median between-group change in total-to-HDL cholesterol ratioat 96 weeks

total and HDL cholesterol plasma concentrations

Mean/median between-group change in waist-to-hip ratioat 96 weeks

umbilical waist and hip measures

Mean/median between-group change in body weightat week 48 and 96

body weight measurement

Mean/median between-group change in maximum umbilical and hip measuresat week 48 and 96

umbilical waist and hip measures

Mean/median between-group change in fasting lipid parametersat weeks 48 and 96

total, HDL, and LDL cholesterol and triglyceride plasma concentrations

Mean/median between-group change in fasting glycaemic parametersat weeks 48 and 96

glucose, insulin, HbA1c concentrations

Mean/median between-group absolute change in limb fat assessed by DXAweek 48 and 96

absolute change from baseline in limb fat

Mean/median between-group percentage change in limb fat assessed by DXAweek 48 and 96

percentage change from baseline in limb fat

Mean/median between-group changes in regional body fat assessed by DXAweek 48 and 96

regional = limb fat and truncal fat

Mean/median between-group changes in total body fat and lean tissue assessed by DXAweek 48 and 96

total body fat and total lean tissue

Mean/median between-group changes in bone mineral content assessed by DXAweek 48 and 96

total bone mineral content

Mean/median between-group change in Body Image questionnaire scoresweeks 48 and 96

NIAID Adult AIDS Clinical Trials Group Baseline and Follow-up questionnaires

Proportion with Metabolic Syndromeweek 0, and week 48 and 96

baseline prevalence and incidence at weeks 48 and 96

Trial Locations

Locations (7)

Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital

🇿🇦

Soweto, Johannesburg, South Africa

Clinical HIV Research Unit, Helen Joseph Hospital

🇿🇦

Westdene, Johannesburg, South Africa

Desmond Tutu HIV Foundation

🇿🇦

Cape Town, South Africa

Chennai Antiviral Research aznd Treatment (CART) Clinical Research Site

🇮🇳

Chennai, India

University of Zimbabwe Clinical Research Centre

🇿🇼

Harare, Zimbabwe

The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Thai Red Cross Research Centre

🇹🇭

Bangkok, Thailand

Univerity of Malaya Medical Centre

🇲🇾

Kuala Lumpur, Malaysia

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