Neurological Monitoring in Patients Switching From Dolutegravir Based Regimen to Bictegravir Based Regimen

Phase 3

• Conditions: HIV-1-infection
• Interventions: Drug: Bictegravir/emtricitabine/tenofovir alafenamide; Drug: Dolutegravir/lamivudine/abacavir

• Registration Number: NCT04155554
• Lead Sponsor: Azienda Ospedaliera Universitaria Senese

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.

Study Timeline

• Study First Submitted: 2019-11-05
• Study First Submitted QC: 2019-11-05
• Study First Posted: 2019-11-07
• Status Verified: 2020-01
• Study Start: 2020-01-29
• Last Update Submitted: 2020-01-29
• Last Update Posted: 2020-01-31
• Primary Completion: 2020-08
• Study Completion: 2021-07

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Bictegravir/emtricitabine/tenofovir alafenamide	Bictegravir/emtricitabine/tenofovir alafenamide	Patients with suppressed viral load switching from dolutegravur/lamivudina/abacavir (50/300/600 mg) 1 tablet OD to bictegravir/emtricitabine/tenofovir alafenamide (50/200/25 mg) 1 tablet OD
Dolutegravir/lamivudine/abacavir	Dolutegravir/lamivudine/abacavir	Patients with suppressed viral load continuing dolutegravir/lamivudine/abacavir (50/300/600 mg) 1 tablet OD

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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).
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 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)
virological failures	12 months	proportion of virological failures and antiretrovirals resistance at virological failure
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)
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).
adverse events	12 months	proportion of adverse events and serious adverse events and of patients discontinuing due to side effects in both arms
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)

Trial Locations

Locations (1)

Barbara Rossetti; 🇮🇹 Siena, Italy