B-free Multistage Trial

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

Keywords

ClinConnect Summary

Life expectancy of persons living with HIV on antiretroviral therapy (ART) is increasing and drug-drug interactions (DDI) with co-medications are becoming a major concern. Individuals who previously experienced virological failure are at risk of DDI as they are generally treated with ritonavir- or cobicistat-boosted ART. The high potency as well as the favorable safety and pharmacokinetic profile of new antiretroviral drugs, including dolutegravir (DTG) and doravirine (DOR), support their evaluation as part of un-boosted therapy for individuals with a history of virological failure. In this...

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.