Clinical trial NCT01449006: A Study of the Neurological Effects of Adding Maraviroc to HAART Regimen in Patients With HIV (HANDmac)
Official title: A Randomised Controlled Clinical Trial of the Efficacy of HAART Intensification With Maraviroc in HIV Virally Suppressed Patients With Cognitive Impairment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Human Immunodeficiency Virus (HIV)
HIV Associated Neurocognitive Disorders (HAND)
Keywords: HIV
HAND
Maraviroc
Neurocognitive
Neurology
Human Immunodeficiency Virus
HIV Associated Neurocognitive Disorders
Lead sponsor: St Vincent's Hospital, Sydney
Sponsor class: OTHER
Collaborators: name: ViiV Healthcare
First posted: 2011-10-07
Enrollment: 19
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 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)

Primary outcomes:
measure: Change in Neurocognitive Functioning
timeFrame: Baseline, 6-months and 12-months
Secondary outcomes:
measure: Change in CSF Neopterin Concentration
timeFrame: Baseline and 12-months
measure: Change in MRS Cerebral Metabolite Ratios in Basal Ganglia
timeFrame: Baseline and 12 months
measure: Change in MRS Cerebral Metabolite Ratios in Frontal White Matter
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, Australia
name: Bruce J Brew, MBBS, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.