B/F/TAF vs Atripla Double-Blind Switch Study in HIV-1 Infected Adults

Study Overview
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Brief Summary
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Atripla (ATP: FTC/TDF/EFV) was the first single pill treatment for HIV and was the most prescribed first-line treatment from approximately 2008 to 2013 for people infected with HIV. However, ATP has not been recommended as a preferred treatment for HIV since 2015, due to there now being single pill treatments that work better. There are a lot of people who are still taking ATP and it is working for them. However, it has the potential to cause serious side effects (chronic kidney disease and fractures and serious neurological effects). These side effects are caused by components in ATP (namely the TDF and EFV parts). Also, the efavirenz (EFV) component is not compatible for treatment of Hepatitis C (HCV) - which is often also seen in people who have HIV. For these reasons, there is a need to find a better alternative treatment for these people currently being treated with ATP.

Detailed Description
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B/F/TAF (bictegravir/FTC/TAF) is an investigational single pill drug treatment drug that contains neither TDF nor EFV. This study is looking at whether changing people to this new drug treatment will continue to suppress their HIV and have fewer side effects.

Official Title
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Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of Switching From Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate to Bictegravir/ Emtricitabine/Tenofovir Alafenamide in HIV-1 Infected Virologically Suppressed Adults

Conditions
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HIV-1-infection

Intervention / Treatment
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* Drug: B/F/TAF
* Drug: Atripla
* Drug: B/F/TAF Placebo
* Drug: Atripla Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-1 seropositive Age > 21 years Receiving ATP > 2 years as their only ART, with HIV-1 RNA < 50 copies/mL at screening and all HIV-1 RNA tests < 100 copies/mL in the past 18 months No documented resistance mutations to the components of ATP Any CD4 count, but no active AIDS-defining opportunistic infections or cancers HBsAg+ permitted if plasma HBV DNA is unquantifiable and the patient does not have decompensated liver disease Exclusion Criteria: Pregnancy, breastfeeding or planned pregnancy in the next 2 years Documented resistance to the components of ATP Active AIDS-defining opportunistic infection or cancer Cancer in past 3 years, except non melanoma skin cancer Active psychotic disease or active depression that may interfere with study participation according investigator discretion Any illness with a life expectancy less than 2 years eGFR < 50 mL/min Urine protein/creatinine > 40 mg/mmoL Patients who the investigator feels are unlikely to commit to the study requirements for any reason Prescription drug therapy for osteoporosis (calcium and/or vitamin D is allowed)

Ages Eligible for Study
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Minimum Age: 21 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: B/F/TAF<br>B/F/TAF + Atripla Placebo Each pill is taken once daily, (total of 2 tablets) The blinded treatment phase of this study will last for 52 weeks | Drug: B/F/TAF<br>* B/F/TAF (Bictegravir 50mg/ Emtricitabine 200mg/ Tenofovir Alafenamide 25mg) Tablet taken orally once daily<br>* Other names: BIKTARVY®;Drug: Atripla Placebo<br>* Tablet taken orally once daily<br>|
| Active Comparator: Atripla<br>Atripla + B/F/TAF Placebo Each pill is taken once daily, (total of 2 tablets) The blinded treatment phase of this study will last for 52 weeks | Drug: Atripla<br>* Atripla (Efavirenz 600mg/ emtricitabine 200 mg/ tenofovir disoproxil 245 mg) Tablet taken orally once daily<br>Drug: B/F/TAF Placebo<br>* Tablet taken orally once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urine Albumin/Creatinine Ratio (UACR) | change in urine albumin/creatinine ratio (UACR) | Baseline and week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HIV-1 RNA | Number of participants with HIV-1 RNA < 50 copies/mL | Week 48 | 
| Efavirenz (EFV) Symptom Scores | change in EFV symptom scores from Pittsburgh Sleep Quality Questionnaire (PSQI) global score. PSQI is a self-rated questionnaire which assesses sleep quality and disturbances over a 1-month time interval. The PSQI global score has a possible range of 0-21. Higher scores represent worse sleep quality. | Baseline and week 4 | 
| Urine Protein/Creatinine Ratio (UPCR) | change in urine protein/creatinine ratio (UPCR) | Baseline and week 48 | 
| Estimated Glomerular Filtration Rate (eGFR) | change in estimated glomerular filtration rate (eGFR) | Baseline and week 48 | 
| Bone Mineral Density (BMD) at the Hip | change in bone mineral density (BMD) at the hip | Baseline and week 48 | 
| Bone Mineral Density (BMD) at the Spine | change in bone mineral density (BMD) at the spine | Baseline and week 48 | 
| CD4 Lymphocyte Counts | change in CD4 lymphocyte counts | Baseline and week 48 | 
| Serum Lipids | change in serum lipids | Baseline and week 48 | 
| Adverse Events | number of adverse events | Baseline, week 4, week 12, week 24, week 36, and week 48 |