Switching From Efavirenz/Atripla to Rilpivirine Among Patients With Neurocognitive or Neuropsychological Side Effects (SWEAR)

A Pilot Randomized Controlled Trial of Switch to Tenofovir Disoproxil Fumarate/Emtricitabine/Rilpivirine (TDF/FTC/RPV) Versus Continue TDF/FTC/Efavirenz (EFV) Treatment Among Virologically Suppressed, HIV-1 Infected Subjects With Mild or Asymptomatic EFV-related Neurocognitive or Neuropsychological Side Effects

Despite long-term use in clinical practice, chronic treatment with efavirenz (EFV) has been associated with persistent central nervous system symptoms or mild or even asymptomatic neurocognitive impairment. Whether switching to rilpivirine (RPV) containing regimen is beneficial among patients who experience mild or asymptomatic neurocognitive/neuropsychiatric adverse events during EFV has not been explored yet.

The proposed pilot study will examine whether switching from single tablet regimen TDF/FTC/EFV to single tablet regimen TDF/FTC/RPV is associated with neurocognitive/neuropsychiatric improvement among HIV-infected patients with mild/asymptomatic neurocognitive impairment or neuropsychiatric symptoms during EFV-containing antiretroviral treatment.

Patients under stable treatment with TDF/FTC/EFV, confirmed HIV-1 RNA viral load < 50 copies/mL and altered scores in depression, quality of sleep or anxiety tests and/or alteration in 1 or more domains as assessed by neuropsychological assessment, will be randomized to immediate or deferred (24 weeks) switch to TDF/FTC/RPV. Neurocognitive and neuropsychiatric tests will be repeated after 12, 24 and 48 weeks of follow-up and variations will be compared between groups.

Study Overview

• Status: Completed
• Conditions: Quality of Life; HIV-1 Infection; Impaired Cognition; Poor Quality Sleep; Depression/Anxiety
• Intervention / Treatment: Drug: Immediate switch to TDF/FTC/RPV; Drug: Switch to TDF/FTC/RPV after 24 weeks

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Brescia, Italy
    • Spedali Civili - University of Brescia
  • Genova, Italy
    • Clinica di Malattie Infettive, Ospedale San Martino
  • Milan, Italy
    • AO San Paolo - University of Milan
  • Torino, Italy
    • Ospedale Amedeo di Savoia - University of Turin
  • MB
    • Monza, MB, Italy, 20900
      • Clinic of Infectious Diseases, AO San Gerardo

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:

• Age ≥18 years old and ability to sign informed consent
• Continuative treatment with TDF/FTC/EFV for ≥180 days
• HIV-1 RNA viral load < 50 copies/mL in two consecutive determinations (including screening)
• No history of treatment failure and/or evidence of any mutations associated with resistance to NRTI or NNRTI
• No contraindication to treatment with study drugs

• Any one of the following conditions:

  (i) Altered scores in depression, quality of sleep or anxiety tests (ii) Alteration in 1 or more domains as assessed by neuropsychological assessment

Exclusion Criteria:

• Ongoing treatment or predictable need of treatment with proton pump inhibitors
• New AIDS defining condition diagnosed within the 21 days prior to screening
• Previous diagnosis of AIDS dementia complex
• Current alcohol or substance dependence
• Major psychiatric disorders
• Decompensated cirrhosis
• Plasma creatinine >1.2 mg/dl or estimated glomerular filtration rate <60 ml/min (MDRD formula)
• AST, ALT or plasma bilirubin >3 times upper limit of normal
• Any other clinical condition or prior therapy that would make the subject unsuitable for the study or unable to comply with the dosing/food requirements

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: Immediate Switch; Immediate switch to TDF/FTC/RPV	Drug: Immediate switch to TDF/FTC/RPV; Other Names: Eviplera (r)
Active Comparator: Deferred Switch; Switch to TDF/FTC/RPV after 24 weeks	Drug: Switch to TDF/FTC/RPV after 24 weeks; Patients will continue current EFV-containing regimen up to week 24 and then will be switched to TDF/FTC/RPV; Other Names: Eviplera(r)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neuropsychiatric side effects	Proportion of patients with improvement in depression, anxiety or quality of sleep scores, evaluated either as a binary (Yes/No) or on a continuous scale	24 weeks
Neurocognitive side effects	- Proportion of patients with improvement in neurocognitive performances in either one of the 7 domains investigated, evaluated either as a binary (Abnormal/Normal) or on a continuous scale (deficit score)	24 weeks
Composite neuropsychiatric/neurocognitive	Proportion of patients with improvement in either one of the previous binary end-point (composite end-point)	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptoms	Proportion of patients with self-reported improvement in treatment-related symptoms	24 weeks
Quality of Life	Proportion of patients with self-reported improvement in quality of life	24 weeks
Cognitive failure	Proportion of patients with improvement in Cognitive Failure Questionnaire	24 weeks
Viral suppression	Proportion of patients with HIV-RNA <50 copies/ml after 12 weeks of treatment (ITT-M=F)	12 weeks
Viral failure	Proportion of patients with HIV-RNA <400 copies/ml after 12 weeks (ITT-M=F)	12 weeks
Virological efficacy	Proportion of patients with HIV-RNA <50 copies/ml after 24 weeks (ITT-M=F)	24 weeks
Safety & Tolerability	Proportion of patients discontinuing treatment for intolerance to study drugs or due to side effects	24 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Resistance	Number of patients with genotypic resistance at failure	12 & 24 weeks
Immunological response	Change From Baseline in CD4+ and CD8+ T-Lymphocyte Cell Counts at Weeks 12 and 24	12 & 24 weeks

Collaborators and Investigators

• Sponsor: Azienda Ospedaliera San Gerardo di Monza
• Collaborators: Gilead Sciences
• Investigators: Principal Investigator: Giuseppe Lapadula, MD, PhD, AO San Gerardo of Monza; Study Director: Andrea Gori, MD, AO San Gerardo of Monza

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2015
• Primary Completion (Actual): July 3, 2017
• Study Completion (Actual): January 15, 2018

Study Registration Dates

• First Submitted: January 20, 2014
• First Submitted That Met QC Criteria: January 20, 2014
• First Posted (Estimate): January 22, 2014

Study Record Updates

• Last Update Posted (Actual): July 5, 2018
• Last Update Submitted That Met QC Criteria: July 2, 2018
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction
• Other Study ID Numbers: IN-IT-264-1331