Efficacy of Rilpivirine-based Regimens as Switch Therapy From Nevirapine-based Regimens in HIV-infected Patients

Efficacy of Rilpivirine-based Regimens as Switch Therapy From Nevirapine-based Regimens in HIV-infected Patients With Complete Virological Suppression: A Randomized Controlled Trial

Background: Nevirapine (NVP)-based antiretroviral therapy (ART) remains to be used in HIV-infected patients in resource limited countries despite its compliance and adverse effect concerns. Rilpivirine (RPV), a newer non-nucleoside reverse transcriptase inhibitor, could be used as an alternative to NVP in virologically suppressed patients. However, there has been limited experience with switching from NVP-based to RPV-based regimens. The investigators aimed to study efficacy and adverse events after ART switching from NVP-based to RPV-based regimens.

Methods: A randomized controlled non-inferiority trial was conducted in HIV-infected patients who received NVP-based regimens and had undetectable plasma HIV RNA for more than 6 months. Patients were randomized 1:1 to continuation arm (NVP-based regimens were continued) or switch arm (NVP-based regimens were switched to RPV-based regimens). Tenofovir disoproxil fumarate (TDF) plus lamivudine (3TC) or emtricitabine (FTC) remained as the backbone of the regimens. Primary endpoint was HIV RNA <40 copies/mL at 48 weeks, with a non-inferiority margin of 12%. Changes of CD4 cell counts and lipid profiles from baseline were analyzed.

Study Overview

• Status: Completed
• Conditions: Efficacy of Rilpivirine-based Regimens as Switch Therapy
• Intervention / Treatment: Drug: Nevirapine; Drug: Rilpivirine

Detailed Description

A single-center randomized controlled, non-inferiority trial to study 48-week treatment outcomes of RPV as a switch therapy was conducted at Ramathibodi Hospital, a tertiary care health center in Thailand from December 2016 to October 2017 Eligible patients who currently received TDF/3TC/NVP (group A) or TDF/FTC/NVP (group B) were block 4 randomly assigned (1:1) by computer-generated random numbers, to continue their current regimen of NVP 200 mg twice daily plus TDF/3TC (group A1) and plus TDF/FTC (groupB1), or to switch from NVP to RPV 25 mg once-daily plus TDF/3TC (group A2) and plus TDF/FTC (groupB2). Patients were advised to take RPV with a meal. Patients were scheduled trial visits at baseline, week 12, 24, 36 and week 48. The laboratory assessment was performed at baseline week 24 and week 48.

• Study Type: Interventional
• Enrollment (Actual): 106
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Thailand
  • Bangkok, Thailand
    • Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Recent plasma HIV-1 RNA viral load within 6 months of the screening that was less than 40 copies/mL, and a CD4 cell count that was more than 200 cells/mm3
• Patient who treated with TDF/FTC/NVP or TDF/3TC/NVP for at least 6 month

Exclusion Criteria:

• patients with a history of HIV drug resistance, patients who used other drugs or drugs which interact with RPV (proton pump inhibitors, histamine H2-receptor antagonists, rifampin, antiepileptic drugs), female patients during pregnancy or breastfeeding, patients whose estimated glomerular filtration rate (eGFR)was <60 mL/min/1.73m2 [by The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) (12)], and patients diagnosed with depressive or psychiatric disorders.

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
Placebo Comparator: continuation arm; patients who currently received TDF/3TC/NVP (group A) or TDF/FTC/NVP (group B) were block 4 randomly assigned (1:1) by computer-generated random numbers, to continue their current regimen of NVP 200 mg twice daily plus TDF/3TC (group A1) and plus TDF/FTC (groupB1)	Drug: Nevirapine; Patients were randomized 1:1 to continuation arm (NVP-based regimens). Tenofovir disoproxil fumarate (TDF) plus lamivudine (3TC) or emtricitabine (FTC) remained as the backbone of the regimens.
Active Comparator: switch arm; patients who currently received TDF/3TC/NVP (group A) or TDF/FTC/NVP (group B) were block 4 randomly assigned (1:1) by computer-generated random numbers to switch from NVP to RPV 25 mg once-daily plus TDF/3TC (group A2) and plus TDF/FTC (groupB2)	Drug: Rilpivirine; Patients were randomized 1:1 to switch arm (NVP-based regimens were switched to RPV-based regimens). Tenofovir disoproxil fumarate (TDF) plus lamivudine (3TC) or emtricitabine (FTC) remained as the backbone of the regimens.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HIV RNA viral load	HIV-1 RNA viral load was performed at 48 by using Amplicor HIV-1 Monitor Test version 1.5 (Roche, Basel, Switzerland)	week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CD4 cell count	blood for CD4 cell count was performed at week 48	week 48
CD4 percentage	blood for CD4 percentage was performed at week 48	week 48
Change of total cholesterol	Change from baseline of total cholesterol was performed at week 48	baseline and week 48
Change of high-density lipoprotein cholesterol level (HDL-c)	Change from baseline of high-density lipoprotein cholesterol level (HDL-c) was performed at week 48	baseline and week 48
Change of low-density lipoprotein cholesterol level (LDL-c)	Change from baseline of low-density lipoprotein cholesterol level (LDL-c) was performed at week 48	baseline and week 48
Change of triglyceride	Change from baseline of triglyceride was performed at week 48	baseline and week 48

Collaborators and Investigators

• Sponsor: Mahidol University

Publications and helpful links

General Publications

• Hagins D, Orkin C, Daar ES, Mills A, Brinson C, DeJesus E, Post FA, Morales-Ramirez J, Thompson M, Osiyemi O, Rashbaum B, Stellbrink HJ, Martorell C, Liu H, Liu YP, Porter D, Collins SE, SenGupta D, Das M. Switching to coformulated rilpivirine (RPV), emtricitabine (FTC) and tenofovir alafenamide from either RPV, FTC and tenofovir disoproxil fumarate (TDF) or efavirenz, FTC and TDF: 96-week results from two randomized clinical trials. HIV Med. 2018 Nov;19(10):724-733. doi: 10.1111/hiv.12664. Epub 2018 Aug 12.
• Taramasso L, Tatarelli P, Ricci E, Madeddu G, Menzaghi B, Squillace N, De Socio GV, Martinelli C, Gulminetti R, Maggi P, Orofino G, Vichi F, Di Biagio A, Bonfanti P; CISAI Study Group. Improvement of lipid profile after switching from efavirenz or ritonavir-boosted protease inhibitors to rilpivirine or once-daily integrase inhibitors: results from a large observational cohort study (SCOLTA). BMC Infect Dis. 2018 Jul 31;18(1):357. doi: 10.1186/s12879-018-3268-5.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2016
• Primary Completion (Actual): October 31, 2017
• Study Completion (Actual): October 31, 2017

Study Registration Dates

• First Submitted: August 16, 2018
• First Submitted That Met QC Criteria: September 6, 2018
• First Posted (Actual): September 10, 2018

Study Record Updates

• Last Update Posted (Actual): September 10, 2018
• Last Update Submitted That Met QC Criteria: September 6, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: rilpivirine switch therapy
• Additional Relevant MeSH Terms: 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 Inducers; Cytochrome P-450 CYP3A Inducers; Nevirapine; Rilpivirine
• Other Study ID Numbers: 10-59-04

Drug and device information, study documents

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