A Study of the Neurological Effects of Adding Raltegravir to HAART Regimen in Patients With HIV (HANDral)
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.
Human Immunodeficiency Virus (HIV)
HIV Associated Neurocognitive Disorders (HAND)
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Randomised Controlled Clinical Trial of the Efficacy of HAART Intensification With Raltegravir in HIV Virally Suppressed Patients With Cognitive Impairment|
- Neurocognitive Function [ Time Frame: Change from baseline neuropsychological testing, at 6 months, and at 12 months ] [ Designated as safety issue: No ]The primary endpoint is improvement on overall neuropsychological performance defined as a reliable change score index (RCI) corrected for practice effect.
- Cerebrospinal Fluid [ Time Frame: Change in Neopterin concentrations in CSF from baseline to 12 months ] [ Designated as safety issue: No ]To determine if there is improvement in CSF neopterin concentrations with the addition of Raltegravir.
|Study Start Date:||October 2011|
|Study Completion Date:||October 2013|
|Primary Completion Date:||October 2013 (Final data collection date for primary outcome measure)|
No Intervention: Standard of Care HAART
Participants randomised to this arm will remain on their standard of care Highly Active Antiretroviral Therapy (HAART).
Participants randomised to this arm will remain on their standard of care Highly Active Antiretroviral Therapy (HAART) with the addition of Raltegravir 400 mg twice daily (BID).
Oral raltegravir, 400 mg tablet, twice daily for one year.
|Australia, New South Wales|
|St. Vincent's Hospital|
|Sydney, New South Wales, Australia, 2010|
|The Alfred Hospital|
|Melbourne, Victoria, Australia, 3181|
|Principal Investigator:||Bruce J Brew, MBBS, PhD||St Vincent's Hospital, Sydney|