HIV-1-infection
Conditions
Keywords
HIV, Neurocognitive functions, Neuropsychiatric side effects, Bictegravir, INSTI
Brief summary
Prospective, randomized study (1: 1), open-label, controlled, phase 3, multicenter, non-profit. The hypothesis of the present study is that bictegravir is associated with a lower incidence and severity of neuropsychiatric symptoms than dolutegravir.
Detailed description
Prospective, randomized study (1: 1), open-label, controlled, phase 3, multicenter, non-profit. The hypothesis of the present study is that bictegravir is associated with a lower incidence and severity of neuropsychiatric symptoms than dolutegravir. The main outcome measure will be a global severity index (GSI) of neuropsychiatric symptoms arising from 10 symptom domains, including somatization, obsessive-compulsiveness, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, psychoticism. The secondary outcomes are to compare, between arms and during follow up, neuropsychiatric symptoms severity, neurocognitive performance, changes in self-reported symptoms, adherence and HR-QoL, correlation between symptoms (neuropsychiatric and other), drug exposure and HR-QoL, proportion of adverse events, proportion of virological failures and antiretrovirals resistance at virological failure.
Interventions
Switch patients from dolutegravir/lamivudine/abacavir to bictegravir/emtricitabine/tenefovir alafenamide to study neuropsychiatric side effects and neurocognitive function
DRUGDolutegravir/lamivudine/abacavir
Continuing dolutegravir/lamivudine/abacavir to study neuropsychiatric side effects and neurocognitive function
Sponsors
Catholic University of the Sacred Heart
Ospedale Policlinico San Martino
Azienda Ospedaliera San Paolo
Ospedale Amedeo di Savoia
Azienda Ospedaliera Universitaria Senese
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Prospective, randomized study (1: 1), open-label, controlled, phase 3, multicenter, non-profit
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \>18 years * HIV-1 infection * HIV RNA \<50 copies/mL \>12 months (including patients with 1 blip 50-200 cp/mL before screening, not confirmed) * On treatment with dolutegravir/abacavir/lamivudine \>6 months
Exclusion criteria
* Previous AIDS events * Pregnancy or pregnancy plan * Decompensated cirrhosis (B or C CPT status) * Intake of alcohol, substances, other drugs that may affect neurocognitive performances * Necessity to receive drugs that may require dosing adjustment of dolutegravir or bictegravir * Certified diagnosis of major depression, psychosis, history of suicidal attempts * Treatment with antidepressants or antipsychotic drugs * History of virological failure with INSTIs * Lack of knowledge of italian language * Impossibility to obtain informed written consent * HBsAg positivity * Estimated glomerular filtration rate by CK-EPI \<50 mL/min per 1.73 m2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| neuropsychiatric symptoms severity in 3 months | 3 months | change in neuropsychiatric symptoms severity, using the Symptom Checklist-90-R, 3 months after switching to bictegravir or continuing dolutegravir (on treatment analysis). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mini International Neuropsychiatric Interview Plus subscale for suicide risk | 12 months | change in neuropsychiatric symptoms severity, using the Mini International Neuropsychiatric Interview Plus subscale for suicide risk, 3 and 12 months after switching to bictegravir or dolutegravir (on treatment analysis). Suicide risk (five questions, score range 0-33 points) in the last 30 days was classified as low (1-5), moderate (6-9), or high (10). |
| neurocognitive performance | 12 months | change in neurocognitive performance, using a comprehensive and validated neuropsychological battery, 12 months after switching to bictegravir or dolutegravir (on treatment analysis). The neurocognitive performance is calculated by averaging the individual deficit scores from each neurocognitive test. Deficit scores for each test were calculated from age-, education-, -adjusted raw scores. |
| neurocognitive impairment and neuropsychiatric symptoms | 12 months | comparison of the inter-arm and intra-arm incidence of neurocognitive impairment (on the basis of Frascati criteria) at 12 months and neuropsychiatric symptoms (using the Symptom Checklist-90-R) at 3 (on treatment analysis) and 12 months (ITT-exposed, using LOCF) |
| self-reported symptoms (21 items, 0-5 points for each), adherence (0-100%) and HR-QoL (9 items, 0-5 points for each) | 12 months | changes in self-reported symptoms, adherence and HR-QoL (using validated questionnaires) during the first year of follow up (ITT-exposed, using LOCF). |
| neuropsychiatric symptoms severity in 3 and 12 months | 12 months | change in neuropsychiatric symptoms severity, each of the 10 symptoms analyzed separately using the Symptom Checklist-90-R, 3 and 12 months after switching to bictegravir or dolutegravir (on treatment analysis) |
| adverse events | 12 months | proportion of adverse events and serious adverse events and of patients discontinuing due to side effects in both arms |
| virological failures | 12 months | proportion of virological failures and antiretrovirals resistance at virological failure |
| Treatment Satisfaction | 12 months | change in Treatment Satisfaction between arms as per specific questionnaire (TSQM Version 1.4, 15 questions, from 0 to 79 points as maximum) |
| drug exposure | 12 months | correlation between symptoms (neuropsychiatric and other), drug exposure and HR-QoL during the first year of follow up (ITT-exposed, using LOCF). |
Countries
Italy
Contacts
Primary ContactBarbara Rossetti, PhD
Backup ContactMaurizio Zazzi, Prof
Outcome results
None listed