A Study of the Neurological Effects of Adding Maraviroc to HAART Regimen in Patients With HIV (HANDmac)

NCT ID: NCT01449006

Last Updated: 2019-02-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-10-31
• Study Completion Date: 2014-09-30

Brief Summary

HIV related cognitive impairment still occurs despite highly active antiretroviral therapy (HAART). HIV disease affects the brain in 20-40% of patients with advancing HIV disease; leading to varying degrees of cognitive impairment, recently termed HIV associated neurocognitive disorders (HAND). HAND may occur in patients who are virally suppressed in both blood and CSF.

Patients with HIV Associated Neurocognitive Disorders (HAND) who are virally suppressed in both their blood and cerebrospinal fluid (CSF), whilst on a highly active antiretroviral therapy (HAART) regimen may have significant cognitive improvement with HAART intensification with the medication Maraviroc; compared to those who remain on their existing regimen.

This study will be a prospective, interventional, randomised and unblinded controlled clinical trial. The aim of this study will be to determine whether HAART intensification with the medication Maraviroc, leads to significant improvement in HIV associated neurocognitive disorders (HAND).

Patients with the recent progression (within 6 months) of HAND (validated by neuropsychological assessment) on HAART, who are virally suppressed (<50 copies per ml) in blood and CSF will be randomised to have their existing HAART regimen intensified with Maraviroc, or not. The control arm will remain on their medication regimen as prescribed. The target is to enrol 70 patients into the control group, and 70 patients into the Maraviroc intensification group.

Patients will undergo baseline neuropsychological testing, MRI, blood tests, and cerebrospinal fluid (CSF) tests (via a lumbar puncture). The methods used to determine the effectiveness of adding Maraviroc, will include further neuropsychological assessment at 6 months, and neuropsychological assessment, MRI and CSF assessment again at 12 months.

Neuropsychological testing completed at 6 and 12 months will be completed by a "blind assessor", in that they will have no knowledge of which arm (treatment or control) the participant is enrolled in.

An evaluation (neuropsychological testing) will be performed should the patient deteriorate during the course of the study, as recognised by the patient's managing physician.

At the end of the study protocol (12 months) the patient's HAART therapy will be managed by their primary physician.

Conditions

Human Immunodeficiency Virus (HIV); HIV Associated Neurocognitive Disorders (HAND)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Standard of care HAART regimen

Participants randomised to this arm of the trial will remain on their usual prescribed HAART regimen.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Maraviroc

Participants randomised to this arm will remain on their usual prescribed HAART regimen, with the addition of Maraviroc. Maraviroc will be prescribed according to the Product Information Sheet, with consideration given to background therapy.

Group Type: EXPERIMENTAL

Maraviroc

Intervention Type: DRUG

Maraviroc oral tablet. Dosage: 150 mg twice daily, 300 mg twice daily, or 600 mg twice daily. Dosing will be dependent on the participant's background HAART therapy, and will be in accordance with the product information sheet.

Interventions

Maraviroc

Maraviroc oral tablet. Dosage: 150 mg twice daily, 300 mg twice daily, or 600 mg twice daily. Dosing will be dependent on the participant's background HAART therapy, and will be in accordance with the product information sheet.

Intervention Type: DRUG

Other Intervention Names

Celsentri

Eligibility Criteria

Inclusion Criteria

• HIV Positive
• On HAART, with plasma viral load < 50 copies/ml for previous 12 months or more
• Able to provide informed consent
• HAND diagnosis, with symptom progression within previous 6 months

Exclusion Criteria

• Non-HIV related neurological disorders and active central nervous system (CNS) opportunistic infection (as assessed by full blood count, electrolytes, creatinine, glucose, liver funciton tests, cryptococcal antigen, venereal disease research laboratory (VDRL), MRI brain scan and CSF analysis for cell count, protein, glucose, culture, VDRL and cryptococcal antigen)
• Psychiatric disorders on the psychiatric axis
• Current major depression
• Current substance use disorder, or severe substance use disorder within 12 months of study entry
• Active Hepatitis C Virus (HCV) (detectable HCV RNA)
• History of loss of consciousness > 1 hour
• Non-proficient in English
• Medications known to pharmacologically interact with antiretrovirals (ARVs)
• Currently taking an entry inhibitor
• Pregnancy (as assessed by the urine pregnancy test)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ViiV Healthcare

INDUSTRY

Sponsor Role: collaborator

Bruce Brew

OTHER

Sponsor Role: lead

Responsible Party

Bruce Brew

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Bruce J Brew, MBBS, PhD

Role: PRINCIPAL_INVESTIGATOR

St Vincent's Hospital - Sydney, Australia

Locations

St. Vincent's Hospital

Sydney, New South Wales, Australia

The Alfred Hospital

Melbourne, Victoria, Australia

Countries

Australia

References

Gates TM, Cysique LA, Siefried KJ, Chaganti J, Moffat KJ, Brew BJ. Maraviroc-intensified combined antiretroviral therapy improves cognition in virally suppressed HIV-associated neurocognitive disorder. AIDS. 2016 Feb 20;30(4):591-600. doi: 10.1097/QAD.0000000000000951.

Reference Type: RESULT

PMID: 26825032 (View on PubMed)

Other Identifiers

114560

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

11/066

Identifier Type: -

Identifier Source: org_study_id