Bictegravir/Emtricitabine/Tenofovir Alafenide Plus Doravirine

Study Overview
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Brief Summary
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The current study proposal is an open label observational trial for maintenance of virologic suppression, and is designed as a non- inferiority switch trial. The study will involve approximately 30 patients, which includes a PK arm of approximately 10 patients. The study will also include secondary outcomes of quality of life (QOL) and weight changes Hypothesis: Patients with prior NUC or NNRTI resistance (but not to rilpivirine or doravirine) will maintain their virologic suppression after a drug regimen switch from rilpivirine/emtricitabine/tenofovir alafenamide in combination with dolutegravir, to bictegravir/emtricitabine/tenofovir alafenamide in combination with doravirine. The switch therapy will avoid food interactions, and will be well tolerated by subjects.

Official Title
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An Open Label Study Evaluating the Safety and Efficacy of Switching From Rilpivirine/Emtricitabine/Tenofovir Alafenamide in Combination With Dolutegravir, to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Combination With Doravirine, in Male HIV+ Subjects > 45 Years With Multi-drug Resistant Virus and Virologic Suppression (Documented With at Least One Viral Load Result < 50 Copies Per mL) During the Last 6 Months on Current Therapy

Conditions
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HIV-1-infection

Intervention / Treatment
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* Drug: Bictegravir/emtricitabine/tenofovir alafenamide + Doravirine switch


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV positive Males, age 45 or older Any genotypic or phenotypic resistance except k65R, 69 insertion, integrase resistance, or resistance to rilpivarine or doravirine. Receiving combination antiretroviral regimen of rilpivirine/emtricitabine/tenofovir alafenamide in combination with dolutegravir > 12 months and with viral load <50 copies/ mL on at least one occasion within the six months prior to switch. Suppressed viral load as defined by one plasma HIV RNA level < 50 copies/mL within previous 6 months. Capable of providing informed consent Exclusion Criteria: Any current or prior integrase inhibitor resistance Nucleoside reverse transcriptase (NRTI) mutation 69 insertion or k65R mutation Documented second generation non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance (rilpivirine or doravirine)

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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Male

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Biktarvy + Doravirine Switch<br>bictegravir 50mg/emtricitabine 200mg/tenofovir alafenamide 25mg tablets + doravirine 100mg tablets taken orally once per day | Drug: Bictegravir/emtricitabine/tenofovir alafenamide + Doravirine switch<br>* Safety and efficacy of switching from rilpivirine/emtricitabine/tenofovir alafenamide in combination with dolutegravir, to bictegravir/emtricitabine/tenofovir alafenamide in combination with doravirine in male, 45+ year old subjects. The study will also include secondary outcomes of quality of life (QOL) and weight changes.<br>* Other names: Biktarvy + Pifeltro Switch;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Viral Suppression | Percentage of patients with viral HIV load (VL) <50 and <200 copies/mL at 48 weeks | 48 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerability of study drug | Tolerability of study drugs will be assessed by summarizing the number of AE/SAEs occurring during the study | Week 48 | 
| Change in Body Mass Index | Assess changes in BMI due to treatment switch | Week 48 | 
| Work Productivity and Activity | Improvement in work productivity and activity as measured by Work Productivity and Activity Impairment Questionnaire (WPAI) | Week 48 | 
| PK Assessment | Subject plasma concentration-time data of bictegravir and doravirine will be analyzed using non-compartmental model (WinNonlin®) | Week 4 (+/- 14 days) with time points at predose (-0.5 hr), 0.5, 1, 2, 4, 6, 8, 12, and 24 hours | 
| Adverse Events Assessment | Assess AE's of any grade and relationship to the drug combination occurring in at least 5% of participants or more. | Day 28, Weeks 12, 24, 36, & 48 | 
| Wellbeing Improvement | Improvement in well-being and sleep inventory as measured by The Pittsburgh Sleep Quality Index (PSQI). Minimum score is 0 and maximum score is 21. A higher score indicates worse quality sleep. | Week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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multi-drug resistant