B-free Multistage Trial

Launched by INSEL GRUPPE AG, UNIVERSITY HOSPITAL BERN · Sep 7, 2023

Keywords

ClinConnect Summary

This trial is studying whether people with HIV who have previously had virological failure can switch from a boosted, multi-drug regimen to a booster-free regimen called DOR/DTG/3TC (doravirine daily with dolutegravir/lamivudine) for 48 weeks, and still keep the virus suppressed. It’s a Phase 4, randomized study that compares this booster-free option with continuing their current fully suppressive ART. The researchers also want to see if the booster-free plan reduces drug–drug interactions, and how people feel about treatment, including their quality of life and satisfaction with therapy. A smaller qualitative part will interview about 30 participants to understand their experiences and views on booster-free ART.

If you’re eligible, you’d be an adult living with HIV, currently on an ART regimen that includes a pharmacological booster (like ritonavir or cobicistat) and at least two other non-NRTI drugs, with a history of virological failure and an HIV RNA level under 50 copies/mL for the past 24 weeks. Participants are randomly assigned to either the booster-free DOR/DTG/3TC regimen or to continue their current regimen, for 48 weeks, with regular visits and blood tests. You’d be asked about side effects (including CNS symptoms), kidney and cholesterol health, weight, and quality of life, plus complete surveys about treatment satisfaction. The study is conducted at multiple centers in Switzerland and the Netherlands and is expected to finish around 2027.

Gender

ALL

Eligibility criteria

• • Inclusion criteria
• • Informed consent as documented by signature
• • Age ≥18 years
• • Documented HIV-1 infection
• • On ART including a pharmacological booster (ritonavir or cobicistat) and at least 2 drugs from classes other than NRTI (e.g. non-nucleoside reverse transcriptase inhibitor, integrase-inhibitor, protease inhibitor or entry inhibitor)
• • History of ART change due to virological failure
• • HIV-RNA \<50 cp/mL at screening and for at least 24 weeks before screening, one blip with less than 200 cp/mL allowed
• • Exclusion criteria
• • Creatinine clearance \<30mL/min, calculated using the CKD-EPI formula
• • Known hypersensitivity, allergy, or intolerance to DOR, DTG, or 3TC
• • Presence of major drug resistance mutations against DTG (G118R, G140R, Q148H, Q148K, Q148R, R263K) or DOR (V106A, Y188L, F227C, F227L, M230L, Y318F) according to IAS-USA in individual cumulative resistance analyses. Patients without available resistance testing should not be excluded if no resistance to DTG and/or DOR is assumed based on ART history.
• • Concomitant use of drugs that decrease DTG or DOR blood concentrations
• • Chronic hepatitis B infection, defined as a positive hepatitis B surface antigen (HBsAg) at the screening visit
• • Women who are pregnant or breast-feeding. Women of childbearing potential (women who are not surgically sterilized / hysterectomised and / or post-menopausal for longer than 2 years must have a negative pregnancy test at screening).
• • Participation in another ART intervention study within the 30 days preceding and during the present study.
• • Qualitative sub-study
• • The same inclusion and exclusion criteria as those listed above will be applied. Fifteen persons who were excluded from the trial based on the exclusion criteria above will be recruited for qualitative interviews. In addition to the criteria mentioned above, individuals who are not fluent in German or French will be excluded from the qualitative sub-study.