Phase IV, a Clinical Trial to Assess Safety and Convenience of the Change From DTG/3TC to BIC/FTC/TAF in People With HIV, Good Virological Control and Neuropsychiatric Vulnerabilities

Study Overview
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Brief Summary
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In people infected with HIV, with suppressed HIV viral load and receiving treatment with DTG/3TC: The change to BIC/FTC/TAF will decrease the development of adverse events of neuropsychiatric etiology. The change to BIC/FTC/TAF may improve the patient´s tolerability and degree of acceptance and use of TAR.

Detailed Description
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The clinical trial is designed to compare people with HIV and neuropsychiatric vulnerabilities, the safety and tolerability of switch to BIC/FTC/TAF versus continue on DTG/3TC. The study includes the inclusion of 80 participants with HIV and who present among their personal history any of those established among the selection criteria (insomnia, anxiety or depression), agree to participate in the same The participants, after signing the informed consent and verifying the meeting of the selection criteria, they will be randomized to continue for 48 weeks with DTG/3TC + BIC/FTC/TAF placebo (arm 1) or switch to BIC/FTC/TAF + placebo DTG/3TC (arm 2). All participants, except those who discontinue the study early, must to complete the same schedule of visits. It will be cause of early discontinuation loss to follow-up, withdrawal of consent, or development of any condition that requires discontinuation or change of assigned treatment. During follow-up, the management of the basic neuropsychiatric pathology of each participant will be performed in accordance with normal clinical practice. In no case, the beginning, the change or the cessation of any pharmacological treatment or neuropsychiatric intervention should be affected by their participation in the study. If the situation arises where any participant developed a severe neuropsychiatric adverse effect (grade 3-4), two specialists in psychiatry experts in the management of patients with HIV would be responsible for evaluating them through the review of their medical history and an interview with the participant in person or via telematics. This evaluation will aim to confirm the relevance of the continuity of the patient in the study and the need for further preferential evaluation by psychiatry.

Official Title
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Phase IV, Randomized, Multicenter and Double Clinical Trial Blind Designed to Assess Safety and Convenience of the Change From DTG/3TC to BIC/FTC/TAF in People With HIV, Good Virological Control and Neuropsychiatric Vulnerabilities: MIND Study

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: BIKTARVY 50Mg-200Mg-25Mg Tablet and Dovato placebo
* Drug: Dovato 50Mg-300Mg Tablet + Biktarvy placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult >18 years diagnosed with HIV by standard microbiological techniques Active antiretroviral treatment with DTG/3TC Last HIV viral load performed on the participant in the 6 months prior to the visit screening < 50 copies/mL. If the participant does not have an HIV viral load <50 cop/mL performed in the 14 days prior to the screening visit, it will be necessary to confirm at screening visit that the participant's HIV viral load is <50 cop/mL Prior clinical diagnosis, carried out by a qualified specialist physician, of any of the following pathologies: Insomnia Anxiety disorders Depressive disorders Exclusion Criteria: Allergy or intolerance to any of the components of BIC/FTC/TAF History of active CNS infections Active psychosis or suicidal ideation Pregnant or lactating women, as well as women of childbearing age who do not commit to use at least two contraceptive methods Any clinical or laboratory condition that in the opinion of the investigator will prevent the participant to complete the study procedures Participant included in the neuroimaging substudy: Claustrophobia or presence of magnetizable body devices

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: The drugs used will be drugs for commercial use that contain the active ingredients uses in this study: Experimental regimen: Bictegravir 50mg/ Emtricitabine 200mg/ Tenofovir alafenamide 25mg (combined in a single tablet marketed under the name of Biktarvy®). This regimen is given as 1 tablet once a day. Placebo dolutegravir 50mg/ lamivudine 300mg (combined in a single tablet marketed under the name Dovato®). This regimen istake as 1 tablet once a day. Control regimen: Dolutegravir 50mg/ lamivudine 300mg (combined in a single tablet marketed under the name Dovato®). This regimen is administered as 1 tablet once a day. Placebo bictegravir 50mg/ emtricitabine 200mg/ tenofovir alafenamide 25mg (combined in a single tablet marketed under the name of Biktarvy®). This regimen is given as 1 tablet once a day.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Patients received DTG/3TC + BIC/FTC/TAF placebo<br>DTG 50 mg/3TC 300 mg 1 tablet per day + BIC 50 mg/ FTC 200 mg/ TAF 25 mg placebo 1 tablet per day | Drug: Dovato 50Mg-300Mg Tablet + Biktarvy placebo<br>* The patients randomized to comparador arm will be randomized to Dovato + Biktarvy placebo<br>|
| Experimental: Patients received BIC/FTC/TAF + DTG/3TC placebo<br>BIC 50 mg/ FTC 200 mg/ TAF 25 mg per day + DTG 50 mg/3TC 300 mg placebo1 tablet per day | Drug: BIKTARVY 50Mg-200Mg-25Mg Tablet and Dovato placebo<br>* The patients randomized to experimental arm will be randomized to Biktarvy + Dovato placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The safety of switching to BIC/FTC/TAF versus continuing treatment with DTG/3TC. | Primary endpoint: Proportion of neuropsychiatric adverse effects grade 2-4 (defined using the AIDS Clinical Trials Group Adverse Events Grading Score11) Secondary endpoints: Proportion of grade 2-4 adverse effects (defined using the AIDS Clinical Trials Group Adverse Events Grading Score11) Proportion of ART discontinuations due to neuropsychiatric adverse effects. Proportion of ART discontinuations for any reason. | 24-48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The desirability of switching to BIC/FTC/TAF versus continuing treatment with DTG/3TC. | Primary endpoint: Changes in sleep quality estimated using the Pittsburgh Sleep Quality Questionnaire (PSQI) Secondary endpoints: Changes in mood estimated using the hospital scale of anxiety and depression (HADS) Changes in the scale of satisfaction with ART (ESTAR) Changes in the Spanish version of the MOS HIV quality of life questionnaire. | 24-48 weeks | 
| The efficacy of switching to BIC/FTC/TAF versus continuing treatment with DTG/3TC. | Primary endpoint: Percentage of participants with HIV viral load >50 copies/mL, according to the Snapshot algorithm of the US Food and Drug Administration (margin to demonstrate non-inferiority: 4%) Secondary edpoints: 1)Proportion of participants with HIV viral load <50 copies/mL 2) Proportion of participants with undetectable viral load. 3) Proportion of patients with failure confirmed virology 4) Percentage of patients with virological failure 5) Proportion of participants experiencing blips during the study | 24-48 weeks |