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

Phase 4

Completed

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

• Registration Number: NCT02042001
• Lead Sponsor: Azienda Ospedaliera San Gerardo di Monza

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-01-20
• Study First Submitted QC: 2014-01-20
• Study First Posted: 2014-01-22
• Status Verified: 2014-08
• Study Start: 2015-07-01
• Primary Completion: 2017-07-03
• Study Completion: 2018-01-15
• Last Update Submitted: 2018-07-02
• Last Update Posted: 2018-07-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 74

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Immediate Switch	Immediate switch to TDF/FTC/RPV	Immediate switch to TDF/FTC/RPV
Deferred Switch	Switch to TDF/FTC/RPV after 24 weeks	Switch to TDF/FTC/RPV after 24 weeks

Primary Outcome Measures

Name	Time	Method
Neurocognitive side effects	24 weeks	- 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)
Composite neuropsychiatric/neurocognitive	24 weeks	Proportion of patients with improvement in either one of the previous binary end-point (composite end-point)
Neuropsychiatric side effects	24 weeks	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

Secondary Outcome Measures

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

Trial Locations

Locations (5)

Clinic of Infectious Diseases, AO San Gerardo; 🇮🇹 Monza, MB, Italy

Spedali Civili - University of Brescia; 🇮🇹 Brescia, Italy

Clinica di Malattie Infettive, Ospedale San Martino; 🇮🇹 Genova, Italy

Ospedale Amedeo di Savoia - University of Turin; 🇮🇹 Torino, Italy

AO San Paolo - University of Milan; 🇮🇹 Milan, Italy