A Phase 4 interventional study of NRTIs and Dolutegravir in HIV Infections, sponsored by Kirby Institute. Status unknown at 28 sites in 14 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-04-18.
Sponsored by Kirby Institute · Phase 4, Interventional, and Treatment
D²EFT is a randomised, open-label study in HIV-1 infected patients failing first-line antiretroviral therapy (ART). The study compares 2 regimens of second-line ART (dolutegravir and darunavir pharmaco-enhanced with ritonavir and dolutegravir and 2 prespecified NRTIs) with the WHO recommended regimen of 2NRTIs plus a ritonavir-boosted PI (Standard of Care (SOC)). 1,010 participants from 14 predominantly low-middle income countries will be followed for 96 weeks with the primary endpoint at week 48. The design is based on the hypothesis that one or both of the new regimens will be non-inferior to SOC in terms of virologic control while being easier to take, economically viable and affording simplification of treatment programs.
Consenting participants will be screened and within 45 days randomly allocated to receive either dolutegravir and darunavir/ritonavir, dolutegravir and 2 prespecified NRTIs or the SOC regimen. Participants will be seen four weeks after their randomisation (week 0) visit and then at weeks 12, 24, 48 and 96. Consenting participants will have storage samples collected and cryopreserved at their week 0, 48 \& 96 visits. This repository will be used in future for central baseline resistance testing, pharmacogenomic testing (separate consent required) and has inherent value for later studies of HIV pathogenesis. A 1-time PK sample will be collected at week four for future testing and any participants failing therapy at 24 weeks will have a plasma sample stored for future genotypic resistance testing.
A number of secondary outcomes will be considered in order to compare the performance of the two study treatment regimens. Secondary analyses will focus on virological, immunological, safety, antiretroviral treatment change and medication adherence. A comparison of costs and estimates of cost-effectiveness for the randomised comparison will be a critical component of this study. ART costs will be assessed across study arms. Health-care utilisation will be self-reported and then used to estimate costs. Safety data, viral loads and quality of life data will also be analysed.
The open label nature of the study allows routine care to be undertaken and the use of objective endpoints limit potential bias. The study has well defined and integrated clinical data collection and patient management systems that have been shown to be effective in a wide range of clinical settings.
The choice of NRTIs in the SoC regimen is based on clinical judgement and may be guided by resistance testing if locally available, while those used with dolutegravir are predetermined (tenofovir and lamivudine or emtricitabine). The NRTIs are not provided via the study. At the end of 96 weeks (completion of the protocol) study drug can be offered to all participants for a further 48 weeks as informed by the 48-week study results and clinical judgement. After 144 weeks study drug will no longer be available and composition of the participant's post-study regimen will be the clinician's decision.'
Exclusion Criteria:
The following laboratory variables:
2 x NRTIs + darunavir/ritonavir 800mg/100mg po od
Drug: NRTIs · Drug: Darunavir · Drug: Ritonavir
Dolutegravir 50mg + darunavir/ritonavir 800mg/100mg po od
Drug: Dolutegravir · Drug: Darunavir · Drug: Ritonavir
Dolutegravir 50mg + 2 x NRTIs (tenofovir plus emtricitabine or lamivudine)
Drug: NRTIs · Drug: Dolutegravir
In SOC arm, choice of NRTIs determined by clinician, guided by either genotypic resistance testing or use of a protocol-specified algorithm for N(t)RTI selection. In D2N arm, NRTIs are predetermined.
Also known as: Nucleoside/Nucleotide Reverse Transcription Inhibitors
50mg tablet by mouth once daily for 96 weeks.
Also known as: Tivicay
800mg tablet by mouth once daily for 96 weeks.
Also known as: Prezista
100mg tablet by mouth once daily for 96 weeks.
Also known as: Norvir
The proportion of participants in each arm whose plasma viral load is <50 copies/mL at 48 weeks by intention to treat.
Time frame: At 48 weeks
Proportion with plasma viral load <200 copies/mL
Time frame: At 48 and 96 weeks
Proportion with plasma viral load <50 copies/mL where those stopping randomised therapy for any reason are classified as plasma viral load >50 copies/mL
Time frame: At 48 and 96 weeks
Mean change in CD4+ cell count from baseline
Time frame: At 48 and 96 weeks
Mean/median changes from baseline in fasted lipids (Total cholesterol, LDL-c, HDL-c, and triglycerides)
Time frame: At 48 and 96 weeks
Total number of participants with any serious adverse events (SAEs), and the cumulative incidence of SAEs
Time frame: At 48 and 96 weeks
Total number of opportunistic diseases (AIDS events), deaths and serious non-AIDS defining events and the cumulative incidence of these
Time frame: At 48 and 96 weeks
Adverse events associated with cessation of randomly assigned therapy
Time frame: At 48 and 96 weeks
Categorisation of neuropsychological adverse events
Time frame: At 48 and 96 weeks
Proportion who stopped randomised therapy by reason for stopping
Time frame: At 48 and 96 weeks
Patterns of genotypic HIV resistance associated with virological failure
Time frame: At 48 and 96 weeks
Adherence assessment using participant 7-day recall self-report questionnaire
Time frame: At week 4
Quality of life and anxiety & depression assessed by participant questionnaire
Time frame: At 48 and 96 weeks
Health care utilisation assessed by participant questionnaire
Time frame: At 48 and 96 weeks
Cost of care assessment
Time frame: At 48 and 96 weeks
Plan to share: No
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This study is status unknown, as verified in Sep 2022. You cannot join it, but the record below documents what was studied.
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