A Study of the Neurological Effects of Adding Maraviroc to HAART Regimen in Patients With HIV (HANDmac)
Condition: Human Immunodeficiency Virus (HIV); HIV Associated Neurocognitive Disorders (HAND)
MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections; Immunologic Deficiency Syndromes; Neurocognitive Disorders
Intervention: Maraviroc
Intervention description: 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 MeSH terms: Maraviroc
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 19.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: HIV; HAND; Maraviroc; Neurocognitive; Neurology; Human Immunodeficiency Virus; HIV Associated Neurocognitive Disorders

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.
    

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)