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

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

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.

Study Overview

• Status: Completed
• Conditions: Dyslipidemias; HIV-1-infection; Sustained Virologic Response; Anti-Retroviral Agents; Efavirenz; Rilpivirine
• Intervention / Treatment: Drug: Tenofovir/Emtricitabine/Rilpivirine; Drug: Tenofovir/Emtricitabine/Efavirenz

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 246
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Switching TDF/FTC/EFV to TDF/FTC/RPV; 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; Tenofovir/Emtricitabine/Rilpivirine to compare the non-inferiority of efficacy and adverse effects to Tenofovir/Emtricitabine/Efavirenz in patients with virological suppression; Other Names: TDF/FTC/RPV
Active Comparator: Continuing TDF/FTC/EFV; Continuing Tenofovir 300 mg/day + Emtricitabine 200 mg/day + Efavirenz 600 mg/day Intervention: Tenofovir/Emtricitabine/Efavirenz	Drug: Tenofovir/Emtricitabine/Efavirenz; as a active comparator; Other Names: TDF/FTC/EFV

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Mahidol University
• Investigators: Principal Investigator: Sirichai Wiriyatanakorn, MD, Department of Internal Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University; Principal Investigator: Somneuk Sungkanuparp, MD, Department of Internal Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University

Publications and helpful links

General Publications

• Thai AIDS Society. Thailand National Guidelines on HIV/AIDS Treatment and Prevention 2014. Nontaburi: Bureau of AIDS, TB, and STIs, 2014.
• Molina JM, Cahn P, Grinsztejn B, Lazzarin A, Mills A, Saag M, Supparatpinyo K, Walmsley S, Crauwels H, Rimsky LT, Vanveggel S, Boven K; ECHO study group. Rilpivirine versus efavirenz with tenofovir and emtricitabine in treatment-naive adults infected with HIV-1 (ECHO): a phase 3 randomised double-blind active-controlled trial. Lancet. 2011 Jul 16;378(9787):238-46. doi: 10.1016/S0140-6736(11)60936-7.
• Cohen CJ, Andrade-Villanueva J, Clotet B, Fourie J, Johnson MA, Ruxrungtham K, Wu H, Zorrilla C, Crauwels H, Rimsky LT, Vanveggel S, Boven K; THRIVE study group. Rilpivirine versus efavirenz with two background nucleoside or nucleotide reverse transcriptase inhibitors in treatment-naive adults infected with HIV-1 (THRIVE): a phase 3, randomised, non-inferiority trial. Lancet. 2011 Jul 16;378(9787):229-37. doi: 10.1016/S0140-6736(11)60983-5.
• Thamrongwonglert P, Chetchotisakd P, Anunnatsiri S, Mootsikapun P. Improvement of lipid profiles when switching from efavirenz to rilpivirine in HIV-infected patients with dyslipidemia. HIV Clin Trials. 2016 Feb;17(1):12-6. doi: 10.1080/15284336.2015.1112480. Epub 2016 Jan 7.
• Gianotti N, Poli A, Nozza S, Spagnuolo V, Tambussi G, Bossolasco S, Cinque P, Maillard M, Cernuschi M, Galli L, Lazzarin A, Castagna A. Efficacy and safety in clinical practice of a rilpivirine, tenofovir and emtricitabine single-tablet regimen in virologically suppressed HIV-positive patients on stable antiretroviral therapy. J Int AIDS Soc. 2015 Jul 30;18(1):20037. doi: 10.7448/IAS.18.1.20037. eCollection 2015.

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2016
• Primary Completion (Actual): April 30, 2018
• Study Completion (Actual): April 30, 2018

Study Registration Dates

• First Submitted: August 14, 2017
• First Submitted That Met QC Criteria: August 15, 2017
• First Posted (Actual): August 16, 2017

Study Record Updates

• Last Update Posted (Actual): May 7, 2019
• Last Update Submitted That Met QC Criteria: May 4, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Dyslipidemias; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Tenofovir; Emtricitabine; Efavirenz; Rilpivirine
• Other Study ID Numbers: ID09-59-06

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No