HIV Infections
Conditions
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.
Interventions
DRUGDarunavir (DRV) 800 milligram (MG) Oral Tablet
800 milligrams (mg) orally once daily for 96 weeks
DRUGRitonavir 100 MG Oral Tablet
100 mg orally once daily for 96 weeks
DRUGN(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
DRUGDolutegravir 50 MG Oral Tablet
50 mg orally once daily for 96 weeks
DRUGTDF 300 MG Oral Tablet
300 mg orally once daily for 96 weeks
DRUG3TC 300 MG Oral Tablet
300 mg orally once daily for 96 weeks. Choice of 3TC or FTC will be determined by clinician
DRUGFTC 200 MG Oral Cap
200 mg orally once daily for 96 weeks. Choice of emtricitabine or lamivudine will be determined by clinician
Sponsors
Kirby Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean/median between-group change in total-to-HDL cholesterol ratio | at 48 weeks | total and HDL cholesterol plasma concentrations |
| Mean/median between-group change in waist-to-hip ratio | at 48 weeks | umbilical waist and hip measures |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean/median between-group changes in bone mineral content assessed by DXA | week 48 and 96 | total bone mineral content |
| Mean/median between-group change in total-to-HDL cholesterol ratio | at 96 weeks | total and HDL cholesterol plasma concentrations |
| Mean/median between-group change in waist-to-hip ratio | at 96 weeks | umbilical waist and hip measures |
| Mean/median between-group change in body weight | at week 48 and 96 | body weight measurement |
| Mean/median between-group change in maximum umbilical and hip measures | at week 48 and 96 | umbilical waist and hip measures |
| Mean/median between-group change in fasting lipid parameters | at weeks 48 and 96 | total, HDL, and LDL cholesterol and triglyceride plasma concentrations |
| Mean/median between-group change in Body Image questionnaire scores | weeks 48 and 96 | NIAID Adult AIDS Clinical Trials Group Baseline and Follow-up questionnaires |
| Mean/median between-group absolute change in limb fat assessed by DXA | week 48 and 96 | absolute change from baseline in limb fat |
| Mean/median between-group percentage change in limb fat assessed by DXA | week 48 and 96 | percentage change from baseline in limb fat |
| Mean/median between-group changes in regional body fat assessed by DXA | week 48 and 96 | regional = limb fat and truncal fat |
| Mean/median between-group changes in total body fat and lean tissue assessed by DXA | week 48 and 96 | total body fat and total lean tissue |
| Mean/median between-group change in fasting glycaemic parameters | at weeks 48 and 96 | glucose, insulin, HbA1c concentrations |
| Proportion with Metabolic Syndrome | week 0, and week 48 and 96 | baseline prevalence and incidence at weeks 48 and 96 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Mean/median between-group change in serum biomarker concentrations | weeks 48 and 96 | biomarkers to be determined |
Countries
India, Malaysia, South Africa, Thailand, Zimbabwe
Outcome results
None listed