Clinical trial NCT02042001: Switching From Efavirenz/Atripla to Rilpivirine Among Patients With Neurocognitive or Neuropsychological Side Effects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Impaired Cognition
Depression/Anxiety
Poor Quality Sleep
Quality of Life
HIV-1 Infection
Lead sponsor: Azienda Ospedaliera San Gerardo di Monza
Sponsor class: OTHER
Collaborators: name: Gilead Sciences
First posted: 2014-01-22
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Neuropsychiatric side effects
timeFrame: 24 weeks
measure: Neurocognitive side effects
timeFrame: 24 weeks
measure: Composite neuropsychiatric/neurocognitive
timeFrame: 24 weeks
Secondary outcomes:
measure: Symptoms
timeFrame: 24 weeks
measure: Quality of Life
timeFrame: 24 weeks
measure: Cognitive failure
timeFrame: 24 weeks
measure: Viral suppression
timeFrame: 12 weeks
measure: Viral failure
timeFrame: 12 weeks
measure: Virological efficacy
timeFrame: 24 weeks
measure: Safety & Tolerability
timeFrame: 24 weeks
Other outcomes:
measure: Resistance
timeFrame: 12 & 24 weeks
measure: Immunological response
timeFrame: 12 & 24 weeks
Locations:
city: Monza
country: Italy
facility: Clinic of Infectious Diseases, AO San Gerardo
state: MB
city: Brescia
country: Italy
facility: Spedali Civili - University of Brescia
city: Genova
country: Italy
facility: Clinica di Malattie Infettive, Ospedale San Martino
city: Milan
country: Italy
facility: AO San Paolo - University of Milan
city: Torino
country: Italy
facility: Ospedale Amedeo di Savoia - University of Turin
Study officials:
affiliation: AO San Gerardo of Monza
name: Giuseppe Lapadula, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: AO San Gerardo of Monza
name: Andrea Gori, MD
role: STUDY_DIRECTOR
References: