Dolutegravir and Darunavir Evaluation in Adults Failing Therapy

• Status: Recruiting
• Trial end date: 2023-12-31
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Kirby Institute
• Collaborators: Janssen Pharmaceutica; National Health and Medical Research Council, Australia; National Institute of Allergy and Infectious Diseases (NIAID); UNITAID; ViiV Healthcare
• Treatments: Darunavir; Dolutegravir; Ritonavir

Criteria

Inclusion Criteria:

1. HIV-1 positive by licensed diagnostic test

2. Aged ≥16 years of age (or minimum age as determined by local regulations or as legal requirements dictate)

3. Failed first-line non-nucleoside reverse transcriptase inhibitor (NNRTI) + 2N(t)RTI combination therapy according to virological criteria, defined as at least two consecutive (≥7 days apart) pVL results >500 copies/mL after a minimum period of exposure to continuous NNRTI + 2N(t)RTI first-line therapy of 24 weeks (only the second pVL result needs to be within 45 days of randomisation)

4. For women of child-bearing potential, willingness to use appropriate contraception

5. Able to provide written informed consent

Exclusion Criteria:

1. The following laboratory variables:

1. absolute neutrophil count (ANC) <500 cells/µL

2. haemoglobin <7.0 g/dL

3. platelet count <50,000 cells/µL

4. AST and/or ALT ≥5xULN OR ALT ≥3xULN and bilirubin ≥1.5xULN (with >35% direct bilirubin)

2. Change in antiretroviral therapy within 12 weeks prior to randomisation

3. Prior exposure to HIV protease inhibitors and/or HIV integrase inhibitors

4. Patients with chronic viral hepatitis B infection defined by positive serum hepatitis B surface antigen

5. Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy (INR >2.3), hypoalbuminemia (serum albumin <2.8g/dL), esophageal or gastric varices, or persistent jaundice), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)

6. Anticipated need for Hepatitis C virus (HCV) therapy during the study

7. Subject has creatinine clearance of <50 mL/min via CKD-EPI equation

8. Current use of rifabutin or rifampicin

9. Use of any contraindicated medications (as specified by product information sheets)

10. Intercurrent illness requiring hospitalization

11. An active opportunistic disease not under adequate control in the opinion of the investigator

12. Pregnant or nursing mothers

13. Patients with current alcohol or illicit substance use that in the opinion of the investigator might adversely affect participation in the study

14. Patients deemed unlikely by the investigator to be able to remain in follow-up for the protocol-defined period