Clinical trial NCT01448486: A Study of the Neurological Effects of Adding Raltegravir to HAART Regimen in Patients With HIV
Official title: A Randomised Controlled Clinical Trial of the Efficacy of HAART Intensification With Raltegravir in HIV Virally Suppressed Patients With Cognitive Impairment
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Human Immunodeficiency Virus (HIV)
HIV Associated Neurocognitive Disorders (HAND)
Keywords: HIV
HAND
Human Immunodeficiency Virus
Raltegravir
HIV Associated Neurocognitive Disorders
Neuro-HAART
Neurocognitive
Neurology
Lead sponsor: St Vincent's Hospital, Sydney
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2011-10-07
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 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)

Primary outcomes:
measure: Neurocognitive Function
timeFrame: Baseline, 6 months and 12 months
Secondary outcomes:
measure: Cerebrospinal Fluid
timeFrame: Baseline and 12 months
Other outcomes:
Locations:
city: Sydney
country: Australia
facility: St. Vincent's Hospital
state: New South Wales
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
Study officials:
affiliation: St Vincent's Hospital, Sydney
name: Bruce J Brew, MBBS, PhD
role: PRINCIPAL_INVESTIGATOR
References: