A Clinical Trial Comparing the Efficacy of Tenofovir Disoproxil Fumarate/Emtricitabine/Rilpivirine (TDF/FTC/RPV) Versus TDF/FTC/Efavirenz (TDF/FTC/EFV) in Patients With Undetectable Plasma HIV-1 RNA on Current First-line Treatment

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate noninferiority (a new treatment is equivalent to standard treatment) in terms of the percentage of patients who have plasma human immunodeficiency virus-type 1 (HIV-1) ribonucleic acid (RNA) levels less than 400 copies per mL after 48 weeks of randomized treatment with tenofovir disoproxil fumarate/emtricitabine/rilpivirine (TDF/FTC/RPV) versus TDF/FTC/efavirenz (TDF/FTC/EFV).

Detailed Description
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This is a 48-week, multicenter (study conducted at multiple sites), multinational (conducted at different countries), open-label (all people know the identity of the intervention), randomized (the study medication is assigned by chance) study to assess whether tenofovir disoproxil fumarate/emtricitabine/rilpivirine (TDF/FTC/RPV) shows noninferior response rates of human immunodeficiency virus-type 1 (HIV-1) ribonucleic acid (RNA) suppression less than 400 copies per mL, compared with TDF/FTC/efavirenz (TDF/FTC/EFV). The study consists of 3 phases including, the screening phase (of 6 weeks), treatment phase (of 48 weeks), and follow up phase (of 30 to 35 days after the last dose of study medication). During the 48 weeks treatment phase, patients currently with HIV-1 RNA suppression less than 50 copies per mL on their first-line antiretroviral regimen, will be randomized in a 1:1 ratio, in 2 groups, ie, Group 1 (treatment group) and Group 2 (control group). Both these groups will receive a fixed dose combination (FDC) regimen (ie, FDC tablet: one tablet per day) of either TDF/FTC/RPV in Group 1 or TDF/FTC/EFV in Group 2. Patients will return for study visits at Week 4, 12, 24, 36, and 48 during the treatment period, and then every 24 weeks thereafter during the extended treatment period until the last patient has his or her Week 48 (or treatment discontinuation) visit. Safety evaluations for adverse events, clinical laboratory (central and local) tests, electrocardiogram, vital signs, and physical examination will be performed throughout the study. The treatment duration for each patient will be expected to be between 48 and 108 weeks.

Official Title
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A Phase 3b, Randomized, Open-label Clinical Study to Demonstrate Non-inferiority in Virologic Response Rates of HIV-1 RNA Suppression <400 Copies/mL of TDF/FTC/RPV Versus TDF/FTC/EFV in First-line Antiretroviral NNRTI-based Suppressed Patients. Switching At Low HIV-1 RNA Into Fixed Dose Combinations (SALIF)

Conditions
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Human Immunodeficiency Virus-type 1 Infection

Intervention / Treatment
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* Drug: Rilpivirine
* Drug: Efavirenz
* Drug: Tenofovir disoproxil fumarate
* Drug: Emtricitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented human immunodeficiency virus-type 1 (HIV-1) infection Patients who have been receiving first line highly active antiretroviral therapy (HAART) for at least 1 year before the screening visit Patients who have been taking the same ARV combination for at least 8 weeks before the screening visit and are expected to continue on this regimen throughout the screening period. Patients who prefer to change the current HAART regimen for reasons of simplification and/or toxicity of nucleoside/nucleotide reverse transcriptase inhibitor (N[t]RTI) Plasma HIV-1 RNA less than 50 copies per mL and CD4+ cell count higher than 200 per mm3 at the screening visit Agrees to protocol-defined use of effective contraception Exclusion Criteria: History of virologic failure (2 consecutive plasma HIV-1 ribonucleic acid (RNA) more than or equal to 400 copies per mL) while on previous or current ART History of immunologic failure (2 consecutive CD4+ cell counts during HAART treatment falling below the pre-HAART level) History of any primary N[t]RTI or NNRTI mutations Has a previously documented HIV-2 infection Significantly decreased hepatic function or hepatic insufficiency or diagnosed with acute clinical viral hepatitis Diagnosed with Mycobacterium tuberculosis infection Severe laboratory abnormalities Creatinine clearance less than 50 mL per minute Addicted to drug, including alcohol or recreational drugs

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Patients will receive fixed dose combination (FDC) tablet of tenofovir disoproxil fumarate/emtricitabine/rilpivirine with a meal, until Week 48. | Drug: Rilpivirine<br>* Type=exact number, unit=mg, number=25, form=tablet, route=oral. Rilpivirine will be administered in a fixed dose combination along with tenofovir disoproxil fumarate and emtricitabine, as a single dose tablet.<br>* Other names: EDURANT;Drug: Tenofovir disoproxil fumarate<br>* Type=exact number, unit=mg, number=300, form=tablet, route=oral. Tenofovir disoproxil fumarate will be administered in a fixed dose combination along with rilpivirine and emtricitabine in Group 1, and along with efavirenz and emtricitabine in Group 2.<br>Drug: Emtricitabine<br>* Type=exact number, unit=mg, number=200, form=tablet, route=oral. Emtricitabine will be administered in a fixed dose combination along with rilpivirine and tenofovir disoproxil fumarate in Group 1, and along with efavirenz and tenofovir disoproxil fumarate in Group 2.<br>|
| Active Comparator: Group 2<br>Patients will receive FDC tablet of tenofovir disoproxil fumarate/emtricitabine /efavirenz on an empty stomach at bedtime, until Week 48. | Drug: Efavirenz<br>* Type=exact number, unit=mg, number=600, form=tablet, route=oral. Efavirenz will be administered in a fixed dose combination along with tenofovir disoproxil fumarate and emtricitabine, as a single dose tablet.<br>Drug: Tenofovir disoproxil fumarate<br>* Type=exact number, unit=mg, number=300, form=tablet, route=oral. Tenofovir disoproxil fumarate will be administered in a fixed dose combination along with rilpivirine and emtricitabine in Group 1, and along with efavirenz and emtricitabine in Group 2.<br>Drug: Emtricitabine<br>* Type=exact number, unit=mg, number=200, form=tablet, route=oral. Emtricitabine will be administered in a fixed dose combination along with rilpivirine and tenofovir disoproxil fumarate in Group 1, and along with efavirenz and tenofovir disoproxil fumarate in Group 2.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Plasma Human Immunodeficiency Virus - Type 1 Ribonucleic Acid (HIV-1 RNA) Levels Less Than (<) 400 Copies Per Milliliter (Copies/mL) at Week 48 | Percentage of Participants with viral load (plasma HIV-1 RNA levels) less than 400 copies per mL at Week 48, obtained by the modified Food and Drug Administration (FDA) Snapshot method. | Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Plasma HIV-1 RNA Levels < 50 Copies/mL at Week 48 | Percentage of Participants with plasma HIV-1 RNA <50 copies/mL, obtained by the modified Food and Drug Administration (FDA) Snapshot method. | Week 48 | 
| Percentage of Participants With Plasma HIV-1 RNA Levels More Than or Equal to (>=) 400 Copies/mL at Week 48 Based on Time to Loss of Virologic Response (TLOVR) [Non-virologic Failure Censored] Imputation Method. | Percentage of participants with plasma HIV-1 RNA levels analysed based on time to loss of virologic response (TLOVR) imputation method which is defined as confirmed plasma HIV-1 RNA >=400 copies/mL, excluding participants who discontinued the study with HIV-1 RNA suppression <400 copies/mL. | Week 48 | 
| Percentage of Participants With Plasma HIV-1 RNA Levels >= 50 Copies Per Milliliter (Copies/mL) at Week 48 Based on Time to Loss of Virologic Response (TLOVR) [Non-virologic Failure Censored] Imputation Method. | Percentage of participants with plasma HIV-1 RNA levels analysed based on TLOVR imputation method which is defined as confirmed plasma HIV-1 RNA >=50 copies/mL, excluding participants who discontinued the study with HIV-1 RNA suppression <50 copies/mL. | Week 48 | 
| Percentage of Participant With Treatment Adherence Based on Tablet Count | In both treatment groups adherence rates assessed by tablet count, the majority of participants had an adherence of >95% (97% and 98% in RPV and EFV treated treatment groups respectively). | Up to 48 Weeks | 
| Number of Participants With Treatment-Emergent Nucleoside Reverse Transcriptase Inhibitor (N[t]RTI) or Nucleoside/Nucleotide Reverse Transcriptase Inhibitor (NNRTI) Mutations | To compare the loss of treatment options, the number of participants with treatment-emergent N[t]RTI or NNRTI mutations, as defined by IAS-USA (2014), after virologic failure were compared between the treatment groups. | Up to Week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RNA, Human immunodeficiency virus-type 1 infection, HIV-1, Infectious diseases, Ribonucleic acid, Tenofovir disoproxil fumarate, Emtricitabine, Rilpivirine, Efavirenz, Edurant, TMC278, R278474, Fixed dose combination