b-free multistage trial

Conditions: HIV; Drug Resistance; Drug Drug Interaction

Summary: 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.

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.

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.

Keywords: hiv doravirine dolutegravir drug resistance drug-drug interaction