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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Efficacy of Rilpivirine-based Regimens as Switch Therapy

Intervention / Treatment
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* Drug: Nevirapine
* Drug: Rilpivirine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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 |
| --- | --- |
| Placebo Comparator: continuation arm<br>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<br>* 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.<br>|
| Active Comparator: switch arm<br>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<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rilpivirine switch therapy