Depression/Anxiety, HIV-1 Infection, Impaired Cognition, Poor Quality Sleep, Quality of Life
Conditions
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.
Interventions
DRUGImmediate switch to TDF/FTC/RPV
DRUGSwitch 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
Sponsors
Gilead Sciences
Azienda Ospedaliera San Gerardo di Monza
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite neuropsychiatric/neurocognitive | 24 weeks | Proportion of patients with improvement in either one of the previous binary end-point (composite end-point) |
| 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) |
| 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
| Measure | Time frame | Description |
|---|---|---|
| Cognitive failure | 24 weeks | Proportion of patients with improvement in Cognitive Failure Questionnaire |
| Viral suppression | 12 weeks | Proportion of patients with HIV-RNA \<50 copies/ml after 12 weeks of treatment (ITT-M=F) |
| Virological efficacy | 24 weeks | Proportion of patients with HIV-RNA \<50 copies/ml after 24 weeks (ITT-M=F) |
| Safety & Tolerability | 24 weeks | Proportion of patients discontinuing treatment for intolerance to study drugs or due to side effects |
| Viral failure | 12 weeks | Proportion of patients with HIV-RNA \<400 copies/ml after 12 weeks (ITT-M=F) |
| 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Resistance | 12 & 24 weeks | Number of patients with genotypic resistance at failure |
| Immunological response | 12 & 24 weeks | Change From Baseline in CD4+ and CD8+ T-Lymphocyte Cell Counts at Weeks 12 and 24 |
Countries
Italy
Outcome results
None listed