A Clinical Trial to Evaluate the Reversibility of Abacavir/Lamivudine/Dolutegravir CNS-Related Neurotoxicity After Switching to Tenofovir/Alafenamide/Emtricitabine/Darunavir/Cobicistat (TAF/FTC/DRV/c) (DETOX)

Phase IV, Open Label, Randomized, Clinical Trial to Evaluate the Reversibility of Abacavir/Lamivudine/Dolutegravir CNS-Related Neurotoxicity After Switching to Tenofovir Alafenamide/Emtricitabine/Darunavir/Cobicistat

A phase IV, multicentre, randomised, open-label, pilot clinical trial to evaluate the Reversibility of abacavir/lamivudine/dolutegravir ( ABC/3TC/DTG) CNS-Related Neurotoxicity After Switching to tenofovir alafenamide/emtricitabine/darunavir/cobicistat (TAF/FTC/DRV/c)

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: ABC/3TC/DTG + Symtuza® (TAF/FTC/DRV/c); Drug: Symtuza® (TAF/FTC/DRV/c)

Detailed Description

The investigators estimate that 55 participants will need to be included per group, 110 patients in total, to demonstrate the benefit of switching ABC/3TC/DTG to TAF/FTC/DRV/c

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain
    • Hospital Universitario La Paz
  • Madrid, Spain
    • Hospital Infanta Leonor
  • Madrid, Spain
    • Hospital Fundación Jiménez Díaz
  • Madrid, Spain, 28041
    • Hospital Univ. 12 de Octubre
  • Madrid, Spain
    • H. Univ. Príncipe de Asturias
  • Madrid
    • Majadahonda, Madrid, Spain
      • Hospital Puerta de Hierro

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 96 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient ≥ 18 years of age diagnosed with HIV using conventional serology techniques.
• Current antiretroviral therapy with ABC/3TC/DTG for at least 4 weeks.
• HIV viral load < 50 copies/mL for at least 24 weeks prior to signing the consent form (confirmed by two assays at least 12 weeks apart with viremia < 50 copies/mL between both). If the patient has a recent routine blood test available (≤ 4 weeks) that includes determining HIV viral load, these results may be used for the screening visit. If this test is not available, or the test is more than four weeks old, viral load will be determined on the day of screening in order to confirm that the patient meets this criterion.
• A positive screening test for sleep disorders detected using the sleep quality index (Pittsburgh ).

Exclusion Criteria:

• Determination of at least one HIV viral load ≥ 50 copies/mL in the last 12 weeks.
• Allergy, intolerance or existence of resistance mutations to any of the components of TAF/FTC/DRV/c.
• History of active CNS infections.
• Active psychosis, major depression with psychotic symptoms or autolytic ideation.
• Dementia or mental retardation.
• Drug use with a diagnosis of abuse or dependence according to DSM-5 criteria.
• Illnesses that may interfere with the study procedures.
• Inability to complete any of the study procedures.
• Pregnant or nursing women, as well as women of childbearing age who do not agree to use an adequate birth control method.
• Patient with documented intolerance or hypersensitivity to the study medication, or who has a contraindication to use it, according to the technical data sheet

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
Active Comparator: Arm 1; Patients who postpone switching from ABC/3TC/DTG to Symtuza® (TAF/FTC/DRV/c) four weeks	Drug: ABC/3TC/DTG + Symtuza® (TAF/FTC/DRV/c); Patients continuing on treatment with DTG/3TC/ABC after the randomization for 4 weeks, and then switch to TAF/FTC/DRV/c for 8 weeks
Experimental: Arm 2; Patients who switch from ABC/3TC/DTG to Symtuza® (TAF/FTC/DRV/c) during the baseline visit	Drug: Symtuza® (TAF/FTC/DRV/c); Treatment with TAF/FTC/DRV/c during 8 weeks since randomized

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients who self-reported insomnia, between HIV-suppressed patients who continue ABC/3TC/DTG and those who switched to TAF/FTC/DRV/c	To compare, between the two arms of the study, changes in the percentage and in the severity of neuropsychiatric symptoms compiled using the Pittsburgh sleep quality index (PSQI). The PSQI contains 19 questions in total. These questions are combined to form seven areas with their corresponding score, each of which shows a range between 0 and 3 points. In all cases, a score of "0" indicates ease, while a score of 3 indicates medium difficulty, within their respective area. The score of the seven areas is finally added for a global score, which ranges from 0 to 21 points. "0" indicates ease of sleep and "21" severe difficulty in all areas	week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the severity of neuropsychiatric symptoms, between HIV-suppressed patients who continue ABC/3TC/DTG and those who switched to TAF/FTC/DRV/c	To compare, between the two arms of the study, changes in the percentage and in the severity of neuropsychiatric symptoms compiled using the ACTG adverse effects scale. Researchers will specifically ask the patient about eleven adverse effects at each visit. Each adverse effect will be documented and graduated, according to the criteria established in the "AIDS Clinical Trials Group (ACTG) Division of AIDS scale (2014)". Each adverse effect will be assigned a score between 0 and 3 points. The Score will include the individual scores for each of the eleven adverse effects collected, as well as the sum of all the individual scores presented by each patient at each study visit	week 4
Changes in the severity of neuropsychiatric symptoms, between HIV-suppressed patients who continue ABC/3TC/DTG and those who switched to TAF/FTC/DRV/c	To compare, between the two arms of the study, changes in the percentage and in the severity of neuropsychiatric symptoms compiled using the hospital anxiety and depression scale. The scale includes 14 questions to evaluate the presence of depressive symptoms during the last week. Each question contains four answers with score between 0 and 3 points. To obtain the results of the questionnaire, the researcher must add the score obtained in the 7 questions of anxiety on the one hand and the 7 questions of depression on the other	week 4
Changes in the severity of neuropsychiatric symptoms potentially associated with the use of ABC/3TC/DTG after switching to TAF/FTC/DRV/c	To evaluate the change in the percentage and in the severity of neuropsychiatric symptoms compiled using the ACTG adverse effects scale	Week 4 and 8 after switching to TAF/FTC/DRV/c
Changes in the severity of neuropsychiatric symptoms potentially associated with the use of ABC/3TC/DTG after switching to TAF/FTC/DRV/c	To evaluate the change in the percentage and in the severity of neuropsychiatric symptoms compiled using the Pittsburg sleep quality index (PSQI)	Week 4 and 8 after switching to TAF/FTC/DRV/c
Proportion and severity of neuropsychiatric symptoms potentially associated with the use of ABC/3TC/DTG after switching to TAF/FTC/DRV/c	To evaluate the change in the percentage and in the severity of neuropsychiatric symptoms compiled using the hospital anxiety and depression scale.	Week 4 and 8 after switching to TAF/FTC/DRV/c
Percentage of virologic failure after switching antiretroviral therapy from ABC/3TC/DTG to TAF/FTC/DRV/c	Virologic failure is defined as the presence of two consecutive HIV viral loads ≥ 50 copies/mL.	Week 8 after switching to TAF/FTC/DRV/c

Collaborators and Investigators

• Sponsor: Fundacion SEIMC-GESIDA
• Collaborators: Janssen-Cilag, S.A.

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2018
• Primary Completion (Actual): June 25, 2020
• Study Completion (Actual): June 25, 2020

Study Registration Dates

• First Submitted: September 8, 2018
• First Submitted That Met QC Criteria: September 25, 2018
• First Posted (Actual): September 26, 2018

Study Record Updates

• Last Update Posted (Actual): June 22, 2022
• Last Update Submitted That Met QC Criteria: June 20, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Nervous System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Poisoning; HIV Infections; Neurotoxicity Syndromes; 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; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Emtricitabine; Cobicistat; Darunavir
• Other Study ID Numbers: GESIDA 10418

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