A Study of the Neurological Effects of Adding Raltegravir to HAART Regimen in Patients With HIV
Condition: Human Immunodeficiency Virus (HIV); HIV Associated Neurocognitive Disorders (HAND)
MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections; Immunologic Deficiency Syndromes; Neurocognitive Disorders
Intervention: Raltegravir
Intervention description: Oral raltegravir, 400 mg tablet, twice daily for one year.
Intervention MeSH terms: Raltegravir Potassium
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: HIV; HAND; Human Immunodeficiency Virus; Raltegravir; HIV Associated Neurocognitive Disorders; Neuro-HAART; Neurocognitive; Neurology

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 Neurological 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 Raltegravir; 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 Raltegravir, leads to significant improvement in HIV associated neurological
      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
      raltegravir 400mg twice daily, or not. The control arm will remain on their medication
      regimen as prescribed. The target is to enrol 110 patients into the control group, and 110
      patients into the Raltegravir intensification group.

      Patients will undergo baseline neuropsychological testing, MRI, blood tests, and cerebral
      spinal fluid (CSF) tests (via a lumbar puncture). The methods used to determine the
      effectiveness of adding Raltegravir, will include further neuropsychological testing at 6
      months; and neuropsychological testing, MRI and CSF assessment 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. The
      decision of the Antiretroviral medication regimen to be used in such a case will be
      determined by the 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 HIV 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 (while on existing
             HAART regimen)

        Exclusion Criteria:

          -  Non-HIV related neurological disorders and active CNS opportunistic infection (as
             assessed by full blood count, electrolytes, creatinine, glucose, LFT's, cryptococcal
             antigen, VDRL, MRI brain scan and CSF fluid analysis for cell count, protein, glucose,
             culture, VDRL and cryptococcal antigen)

          -  Psychiatric disorders on the psychotic axis

          -  Current major depression

          -  Current substance use disorder, or severe substance use disorders within 12 months of
             study entry

          -  Active HCV (detectable HCV RNA)

          -  History of loss of consciousness > 1 hour

          -  Non-proficient in English

          -  Medications known to pharmacologically interact with ARV's

          -  Currently taking an Integrase Inhibitor

          -  Pregnancy (as assessed by the urine pregnancy test)