Effect of SwitChing AtriPla to Eviplera on Neurocognitive and Emotional Functioning

NCT ID: NCT02308332

Last Updated: 2017-10-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 58 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-02-28
• Study Completion Date: 2017-06-30

Brief Summary

This study will evaluate the effects of switching Atripla to Eviplera on neurocognition measured by neuropsychological testing and functional MRI

Detailed Description

Efavirenz, an antiretroviral drug used for the treatment of human immunodeficiency virus 1 (HIV-1) infections, is known for its neurological and psychiatric adverse events. Efavirenz is part of Atripla®, a single tablet regimen (STR), currently the most prescribed antiretroviral drug in the Netherlands. Recently, a new STR has become available, Eviplera® containing a successor of Efavirenz, named Rilpivirin. It has been shown in the phase-3 ECHO and THRIVE studies that Atripla as well as Eviplera have excellent and comparable antiretroviral efficacy in naive HIV-infected patients. Furthermore, data from these studies have shown that Eviplera was associated with fewer neurological and psychiatric adverse events than Atripla over 48 weeks. However, this was only patient reported adverse events, not neuropsychological evaluation. Furthermore, they were treatment naïve for HIV. Moreover, there might be a bias in these kind of switch studies due to the fact that those patients who switch will mostly regard their new combination better than the old one. Contrary, data on the long term impact of Efavirenz on neuropsychological performance and symptoms are conflicting.

Objective: This study aims to investigate the effect of switching from Atripla to Eviplera on neurocognitive performances (neurocognitive testing) and imaging (functional MRI scanning) in virologically suppressed HIV-infected patients.

Conditions

Neurocognitive Decline; HIV Associated Neurocognitive Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Intervention

patients switching from Atripla to Eviplera

Group Type: ACTIVE_COMPARATOR

Eviplera

Intervention Type: DRUG

switch from Atripla to emtricitabine/rilpivirine/tenofovir (Eviplera)

Control

patients remaining on Atripla

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Eviplera

switch from Atripla to emtricitabine/rilpivirine/tenofovir (Eviplera)

Intervention Type: DRUG

Other Intervention Names

emtricitabine/rilpivirine/tenofovir

Eligibility Criteria

Inclusion Criteria

• Male, between 30 and 50 years
• HIV-1 RNA < 50 copies/mL on screening visit
• on Atripla continuously for ≥6 months preceding the screening visit
• Have a HIV genotype prior to starting cART with Atripla with no known resistance to any of the study agents at any time in the past including, but not limited to RT mutations K65R, K101E/P, E138G/K/Q/R, Y181C/I/V, M184V/I and H221Y
• Negative TPHA or VDRL < 12 months prior to the screening visit
• no signs of an acute or chronic hepatitis C infection within the past 12 months before screening as defined in the Dutch guideline (Arends et al. Neth J Med 2011)
• No subjective neurocognitive complaints in the preceding 12 months
• willingness to take Eviplera together with food according to the manufacturer's prescriptions.
• Estimated glomerular filtration rate ≥50 mL/min (Cockcroft-Gault formula) on last routine measurement during outpatient clinic
• able to understand and comply to study procedures and to provide written informed consent

Exclusion Criteria

• Non-native Dutch speakers
• Proven major depression through psychiatric consultation within the past year or on anti-depressant drugs (SSRI or TCA)
• Active or known from medical history past CNS opportunistic infections
• History of proven neurologic disease (e.g. multiple sclerosis, brain tumor, cerebrovascular event, etc)
• Active psychiatric disorders classified according to the DMS V criteria
• History or evidence of alcohol or drug abuse defined according to DSM V criteria
• TSH within normal reference values on last routine measurement during outpatient clinic
• Contraindications for undergoing an MRI; a pacemaker or metallic devices/foreign bodies in situ, proven claustrophobia.

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: collaborator

UMC Utrecht

OTHER

Sponsor Role: lead

Responsible Party

J.E. Arends

Infectious Diseases Physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Joop Arends, MD PhD

Role: PRINCIPAL_INVESTIGATOR

UMC Utrecht

Locations

UMC Utrecht

Utrecht, , Netherlands

Countries

Netherlands

References

Oomen PGA, Hakkers CS, Arends JE, van der Berk GEL, Pas P, Hoepelman AIM, van Welzen BJ, du Plessis S. Underlying Neural Mechanisms of Cognitive Improvement in Fronto-striatal Response Inhibition in People Living with HIV Switching Off Efavirenz: A Randomized Controlled BOLD fMRI Trial. Infect Dis Ther. 2024 May;13(5):1067-1082. doi: 10.1007/s40121-024-00966-7. Epub 2024 Apr 20.

Reference Type: DERIVED

PMID: 38642238 (View on PubMed)

Other Identifiers

ABR50959

Identifier Type: -

Identifier Source: org_study_id