Neurological Monitoring in Patients Switching From Dolutegravir Based Regimen to Bictegravir Based Regimen (DOBINeuro)

The Effects of Switching From Dolutegravir/Lamivudine/Abacavir (d/l/a) to Bictegravir/Emtricitabine/Tenofovir Alafenamide (b/f/Taf) in Patients With Suppressed Viral Load on Neuropsychiatric Side Effects and Neurocognitive Function

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.

Study Overview

• Status: Unknown
• Conditions: HIV-1-infection
• Intervention / Treatment: Drug: Bictegravir/emtricitabine/tenofovir alafenamide; Drug: Dolutegravir/lamivudine/abacavir

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 Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Barbara Rossetti, PhD; Phone Number: +393201437658; Email: barbara.rossetti@ao-siena.toscana.it
• Study Contact Backup: Name: Maurizio Zazzi, Prof; Phone Number: +390577233863; Email: maurizio.zazzi@unisi.it

Study Locations

• Italy
  • Siena, Italy, 53100
    • Recruiting
    • Barbara Rossetti
    • Contact: Barbara Rossetti, PhD; Phone Number: +393201437658; Email: barbara.rossetti@ao-siena.toscana.it
    • Contact: Maurizio Zazzi, Prof; Phone Number: +390577233863; Email: maurizio.zazzi@unisi.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: Bictegravir/emtricitabine/tenofovir alafenamide; Switch patients from dolutegravir/lamivudine/abacavir to bictegravir/emtricitabine/tenefovir alafenamide to study neuropsychiatric side effects and neurocognitive function; Other Names: Biktarvy
Active Comparator: Dolutegravir/lamivudine/abacavir; Patients with suppressed viral load continuing dolutegravir/lamivudine/abacavir (50/300/600 mg) 1 tablet OD	Drug: Dolutegravir/lamivudine/abacavir; Continuing dolutegravir/lamivudine/abacavir to study neuropsychiatric side effects and neurocognitive function; Other Names: Triumeq

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
neuropsychiatric symptoms severity in 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).	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
neuropsychiatric symptoms severity in 3 and 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)	12 months
Mini International Neuropsychiatric Interview Plus subscale for suicide risk	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).	12 months
neurocognitive performance	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.	12 months
neurocognitive impairment and neuropsychiatric symptoms	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)	12 months
self-reported symptoms (21 items, 0-5 points for each), adherence (0-100%) and HR-QoL (9 items, 0-5 points for each)	changes in self-reported symptoms, adherence and HR-QoL (using validated questionnaires) during the first year of follow up (ITT-exposed, using LOCF).	12 months
drug exposure	correlation between symptoms (neuropsychiatric and other), drug exposure and HR-QoL during the first year of follow up (ITT-exposed, using LOCF).	12 months
adverse events	proportion of adverse events and serious adverse events and of patients discontinuing due to side effects in both arms	12 months
virological failures	proportion of virological failures and antiretrovirals resistance at virological failure	12 months
Treatment Satisfaction	change in Treatment Satisfaction between arms as per specific questionnaire (TSQM Version 1.4, 15 questions, from 0 to 79 points as maximum)	12 months

Collaborators and Investigators

• Sponsor: Azienda Ospedaliera Universitaria Senese
• Collaborators: Catholic University of the Sacred Heart; Ospedale Policlinico San Martino; Azienda Ospedaliera San Paolo; Ospedale Amedeo di Savoia
• Investigators: Principal Investigator: Barbara Rossetti, PhD, Azienda Ospedaliera Universitaria Senese

Study record dates

Study Major Dates

• Study Start (Actual): January 29, 2020
• Primary Completion (Anticipated): August 1, 2020
• Study Completion (Anticipated): July 1, 2021

Study Registration Dates

• First Submitted: November 5, 2019
• First Submitted That Met QC Criteria: November 5, 2019
• First Posted (Actual): November 7, 2019

Study Record Updates

• Last Update Posted (Actual): January 31, 2020
• Last Update Submitted That Met QC Criteria: January 29, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: HIV; Bictegravir; Neurocognitive functions; Neuropsychiatric side effects; INSTI
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Tenofovir; Emtricitabine; Emtricitabine tenofovir alafenamide; Lamivudine; Dolutegravir; Abacavir; Triumeq
• Other Study ID Numbers: 2018-004885-32

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No