Switching TDF/FTC/EFV to TDF/FTC/RPV VS Continuing TDF/FTC/EFV in HIV Patients With Complete Virological Suppression

Study Overview
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Brief Summary
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According to the Thai National Guidelines for Treatment of HIV/AIDS 2014, the recommended first line ART regimen was 2 NRTIs backbone, TDF and FTC; plus 1 NNRTI, EFV, with RPV as an alternative one. Most of the randomized-controlled studies, including ECHO and THRIVE, showed the non-inferiority of RPV compared with EFV in naive cases. But there were not much randomized-controlled trials for changing from other NRTI to RPV in patients who currently on another ART, especially in Thailand. Moreover, the concerned adverse effects of dyslipidemia and neurological symptoms were better in RPV-based than EFV-based regimen. Finally, the cost-effectiveness and universal coverage are also the benefit of RPV over EFV in term of economics.

Detailed Description
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According to the Thai National Guidelines for Treatment of HIV/AIDS 2014, the recommended first line ART (Anti-retroviral therapy) regimen was 2 NRTIs (nucleoside reverse transcriptase inhibitors) backbone, which are TDF (Tenofovir) and FTC (Emtricitabine); plus 1 NNRTI (non-nucleoside reverse transcriptase inhibitor), which is EFV (Efavirenz), with RPV (Rilpivirine) as an alternative in this class of drug. Most of the randomized-controlled studies, including ECHO (Rilpivirine versus efavirenz with tenofovir and emtricitabine in treatment-naive adults infected with HIV-1) and THRIVE (Rilpivirine versus efavirenz with two background nucleoside or nucleotide reverse transcriptase inhibitors in treatment-naive adults infected with HIV-1), the major trials about RPV, showed the non-inferiority in efficacy of RPV compared with that of EFV in treatment-naive cases with blood HIV viral load less than 500,000 copies/mL. But there were not many trials focusing on changing the ART-regimens from other NRTI to RPV in patients who currently on another ART, especially in randomized-controlled design. There were some studies comparing continuing current regimens versus changing to Rilpivirine-based regimens, but they didn't exclusively select the homogeneous drug components. In Thailand, study of changing to Rilpivirine-based regimens was primarily designed to evaluate the adverse outcome about dyslipidemia, whereas efficacy was a secondary outcome. Most studies, the concerned adverse effects of dyslipidemia and neurological symptoms were better in RPV-based than EFV-based regimen. Finally, the cost-effectiveness and universal coverage are also the benefit of RPV over EFV in term of economics. Therefore, we design this study to evaluate the efficacy; in term of non-inferiority, of the newer, safer, and cheaper drug, Rilpivirine, to Efavirenz, the general-use drug with acceptable efficacy, in the virological-suppressed patients currently on ART. Besides, we also assess the adverse outcomes and factors associated with successful or failure of treatment. In addition, we can have more backup data in term of national economics.

Official Title
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Switching Tenofovir/Emtricitabine/Efavirenz to Tenofovir/Emtricitabine/Rilpivirine Versus Continuing Tenofovir/Emtricitabine/Efavirenz in HIV1-infected Patients With Complete Virological Suppression

Conditions
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Rilpivirine, Anti-Retroviral Agents, Efavirenz, HIV-1-infection, Sustained Virologic Response, Dyslipidemias

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: on TDF/FTC/EFV for more than 3 months Blood HIV RNA viral load <50 copies/mL CD4+ count >200 cells/mm3 eligible to sign the informed consent Exclusion Criteria: history of NRTI resistance on medication that potentially interact with study drug denied to participate in the study

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: Switching TDF/FTC/EFV to TDF/FTC/RPV<br>Switching from Tenofovir 300 mg/day + Emtricitabine 200 mg/day + Efavirenz 600 mg/day (once daily) to Tenofovir 300 mg/day + Emtricitabine 200 mg/day + Rilpivirine 25 mg/day (once daily) Intervention: Tenofovir/Emtricitabine/Rilpivirine | Drug: Tenofovir/Emtricitabine/Rilpivirine<br>* Tenofovir/Emtricitabine/Rilpivirine to compare the non-inferiority of efficacy and adverse effects to Tenofovir/Emtricitabine/Efavirenz in patients with virological suppression<br>* Other names: TDF/FTC/RPV;|
| Active Comparator: Continuing TDF/FTC/EFV<br>Continuing Tenofovir 300 mg/day + Emtricitabine 200 mg/day + Efavirenz 600 mg/day Intervention: Tenofovir/Emtricitabine/Efavirenz | Drug: Tenofovir/Emtricitabine/Efavirenz<br>* as a active comparator<br>* Other names: TDF/FTC/EFV;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained virological response | maintain the undetectable HIV viral load | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lipid adverse outcome | Different in blood lipid profiles, including triglycerides, cholesterol, HDL, and LDL | 12 months | 
| Neurological adverse outcome | Neurological adverse events such as dizziness | 12 months | 
| Cost -saving after switching regimens |  | 12 months |