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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Impaired Cognition, Depression/Anxiety, Poor Quality Sleep, Quality of Life, HIV-1 Infection

Intervention / Treatment
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* Drug: Immediate switch to TDF/FTC/RPV
* Drug: Switch to TDF/FTC/RPV after 24 weeks


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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

What is the study measuring?
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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 |