B-free Multistage Trial

Официальное название

Booster-free Antiretroviral Therapy for Persons Living With HIV and Multidrug Resistance: A Multicentre Multi-stage Randomized Trial

Обзор

The primary objective of the study is to evaluate the efficacy of a booster-free regimen including DOR/DTG/3TC among HIV-suppressed PLWH with previous virological failure. The key secondary objectives are i) to determine whether switching to DOR / DTG / 3TC leads to lower burden of DDI compared to continuing a booster-containing regimen, and ii) to assess changes in patient perception on treatment acceptability and satisfaction, as well as health-related quality of life after a switch to booster-free ART. Qualitative sub-study: Qualitative objectives will be met using semi-structured interviews. Thirty people (15 from the intervention arm, 15 from the control arm) will be interviewed twice, at week 0 and week 48. Additional 15 individuals from the observational cohort will be interviewed once. Interviews will take place following study visits and performed using semi-structured guides. The guide for the interviews at week 48 will be based on results from analyses of the interviews conducted at week 0.

Подробное описание

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 adaptive trial within the Swiss HIV Cohort Study (SHCS) and partner clinics in the Netherlands, the investigators aim to evaluate the efficacy and acceptability of the booster-free regimen DOR/DTG/3TC for treatment-experienced individuals.

Вмешательства

• Препарат DOR/DTG/3TC
  Doravirine 100 mg (Pifeltro®) will be administered once daily in combination with co-formulated dolutegravir/lamivudine 50/300 mg (Dovato®) for a duration of 48 weeks.

Первичные конечные точки

• Loss of viral suppression [Срок оценки: Week 48]

Вторичные конечные точки (12)

• Changes in DDI score from week 0 to 48 [Срок оценки: Week 0 and 48]
• Patient report outcomes concerning changes in treatment satisfaction between baseline and 48 weeks, as determined using the HIV Treatment Satisfaction Questionnaire HIVTSQc (change version). [Срок оценки: Week 0 to 48]
• Proportion of patients experiencing confirmed virological failure [Срок оценки: Week 48]
• Proportion of individuals detected with new drug resistance [Срок оценки: Week 0 to 48]
• Proportion of individuals with any moderate (orange flag) or severe (red flag) DDI [Срок оценки: Week 0 to 48]
• Proportion of patients with DDI leading to suboptimal management of comorbidities [Срок оценки: Week 0 and 48]
• Patient report outcomes concerning differences in quality of life between both groups at week 48 assessed by the World Health Organization Quality-of-Life- HIV Bref (WHOQOL-HIV BREF) questionnaire [Срок оценки: Week 48]
• Patient report outcomes concerning differences in treatment satisfaction between both groups assessed by HIV Treatment Satisfaction Questionnaires [Срок оценки: Week 48]
• Proportion of individuals reporting depression assessed by Patient Health Questionnaire-9 [Срок оценки: Week 0 and 48]
• Changes in intact proviral HIV-DNA levels [Срок оценки: Week 0 to 48]
• Proportion of individuals who develop a detectable HBV viral load [Срок оценки: Weeks 24 and 48]
• Cumulative cost of all ART drugs used [Срок оценки: Week 0 to 48]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Швейцария · 8 центров

• Cantonal Hospital Aarau — Aarau
• University Hospital Basel — Basel
• Inselgruppe AG — Bern
• University Hospital Geneva — Geneva
• University of Lausanne Hospitals — Lausanne
• Lugano Regional Hospital Lugano — Lugano
• Cantonal Hospital of St. Gallen — Sankt Gallen
• University Hospital Zürich — Zurich

Публикации

• Ballif M, Braun D, Calmy A, Bernasconi E, Cavassini M, Tissot F, Stoeckle M, Schmid P, Fux CA, Van der Valk M, Brinkman K, Mudrikova T, Bonnet F, Leleux O, Saude M, Hirter D, Schwab N, Limacher A, Rintelen F, Kouyos R, Haerry D, Zambrano SC, Egloff M, Akre C, Peytremann-Bridevaux I, Rauch A, Wandeler G, Surial B. Booster-free anti-retroviral therapy for persons living with HIV and multidrug resist PMID 39578038

Идентификаторы

NCT: NCT06037564 · B-free trial - Stage 1

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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