Efficacy of Neuro-HAART in Patients With HIV (HANDobs)

This study has been terminated.
(Slower than expected recruitment)
Sponsor:
Collaborator:
ViiV Healthcare
Information provided by (Responsible Party):
Bruce Brew, St Vincent's Hospital, Sydney
ClinicalTrials.gov Identifier:
NCT01434654
First received: September 12, 2011
Last updated: July 6, 2016
Last verified: July 2016
  Purpose

Patients infected with Human Immunodeficiency Virus (HIV) are at risk of brain related complications despite the use of highly active antiretroviral therapy (HAART). Such complications are termed HIV neurocognitive disorders (HAND) and comprise a spectrum from asymptomatic neurocognitive impairment (ANI), through mild cognitive impairment (MCI) to severe HIV dementia (HAD).

Prior to HAART approximately 30% of patients with advanced HIV disease had cognitive impairment; with HAART the incidence of HAND has decreased but its prevalence increased. The reasons for the ongoing development of cognitive impairment in HAART treated patients are not clear. They might relate to virus induced brain injury prior to starting HAART, the onset of a separate neurological process, toxicity related to HAART, or ongoing viral infection in the brain.

It is clear that the ability of different antiretroviral drugs to penetrate the brain varies but what is not established is whether these differences between drugs lead to different neurological outcomes. The investigators propose to study HIV infected patients stable on HAART for 12 months; subdividing the groups according to the brain penetrance of their drug combination. Patients would undergo neuropsychological assessment and MRI brain scan at the start of the study and after 12 months.

Differences in neuropsychological tests and MRI would be sought between treatment groups to establish whether HAART with better CNS penetration is associated with better outcome and fewer MRI changes.


Condition
HIV

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: The Efficacy of Neuro-HAART in HIV Infected Individuals

Resource links provided by NLM:


Further study details as provided by St Vincent's Hospital, Sydney:

Primary Outcome Measures:
  • Change in Neurocognitive Functioning [ Time Frame: Change from baseline Neuropsychological testing at 6 and 12 months ] [ Designated as safety issue: No ]
    Change in overall neurocognitive performance, defined as a global neurocognitive z-score, after a 12-month period of observation, between HIV positive patients taking antiretroviral regimens categorized as being either of high or low CNS penetration. To derive this score, 1) raw scores obtained from a 5-domain brief neurocognitive battery were converted to age-corrected z-scores (M=0, Standard Deviation=1) and 2) the set of individual subtest z-scores were averaged to generate a single composite (global) z-score for each subject. Lower (negative) scores therefore indicate greater levels of cognitive impairment.


Secondary Outcome Measures:
  • Change in MRS Cerebral Metabolite Ratios in Basal Ganglia [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
    Change in major cerebral metabolites in the basal ganglia, as measured by 1H-Magnetic Resonance Spectroscopy (MRS), after a 12 month period of observation. Spectra were acquired on a Phillips Achieva 3T MRI scanner using point-resolved spectroscopy (PRESS) sequence with short echo time (TE). jMRUI/AMARES algorithm was used to process spectra. Metabolite ratios were calculated for the following metabolites: N-acetyl aspartate (NAA), choline (Cho), creatine (Cr), myo-inositol (mIo), in relation to internal water (H20) as standard.

  • Change in MRS Cerebral Metabolite Ratios in Frontal White Matter [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
    Change in major cerebral metabolites in the frontal white matter, as measured by 1H-Magnetic Resonance Spectroscopy (MRS), between baseline and 12-months. Spectra were acquired on a Phillips Achieva 3T MRI scanner using point-resolved spectroscopy (PRESS) sequence with short TE. jMRUI/AMARES algorithm was used to process spectra. Metabolite ratios were calculated for the following metabolites: N-acetyl aspartate (NAA), choline (Cho), creatine (Cr), myo-inositol (mIo), glutamate/glutamine complex (Glx), in relation to internal H20 as standard.

  • Cerebrospinal Fluid [ Time Frame: Baseline to 12 Months ] [ Designated as safety issue: No ]
    To measure plateaux CSF ARV concentrations. This will identify the proportion of patients achieving levels of specific ARVs capable of inhibiting 95% of in vitro viral replication (IC95).


Biospecimen Retention:   Samples Without DNA
Cerbrospinal fluid and bloods

Enrollment: 19
Study Start Date: September 2011
Study Completion Date: September 2014
Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
Non Neuro-HAART (low CNS penetrance)
Participants will be assessed based on their current Highly Active Antiretroviral Treatment (HAART). A scoring system is utilised to determine if their current treatment has high Central Nervous System (CNS) penetrance or low CNS penetrance. This will determine which study cohort they are allocated to. No treatment adjustments or changes will be made, they will remain on their usual HAART regimen.
Neuro-HAART (high CNS penetrance)
Participants will be assessed based on their current Highly Active Antiretroviral Treatment (HAART). A scoring system is utilised to determine if their current treatment has high Central Nervous System (CNS) penetrance or low CNS penetrance. This will determine which study cohort they are allocated to. No treatment adjustments or changes will be made, they will remain on their usual HAART regimen.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
HIV positive participants on HAART who attend outpatient primary care clinics.
Criteria

Inclusion Criteria:

  • HIV positive with nadir cluster of differentiation 4 (CD4) count <350 /microlitre (uL)
  • Taking HAART with CNS Penetration Effectiveness (CPE) score of either ≤7.0 or ≥7.5 for 1 year or more. Changes in antiretrovirals (ARVs) within the last 12 months are allowed so long as the CPE score does not lead to a change groups
  • Plasma HIV viral load <50 copies / mL for preceding 12 months or longer
  • Informed consent given by participant or legally appointed guardian

Exclusion Criteria:

  • Non-HIV related neurological disorders and active CNS opportunistic infection as assessed by full blood count, electrolytes, creatinine, glucose, liver function tests, cryptococcal antigen, venereal disease reaction level (VDRL), MRI brain scan and cerebrospinal fluid analyses for cell count, protein, glucose, culture, VDRL and cryptococcal antigen.
  • Psychiatric disorders on the psychotic axis, current major depression, and current substance use disorder as assessed by the Study Enrolment Questionnaire for Eligibility
  • Severe substance use disorders (within 12 months of study entry)
  • Active Hepatitis C virus (HCV) (detectable HCV RNA because HCV per se can cause cognitive impairment)
  • History of loss of consciousness >1 hour
  • Non-proficient in English as assessed by the "English as a second language questionnaire"
  • Medications known pharmacologically to interact with ARVs
  • Pregnancy as assessed by the urinary pregnancy test
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01434654

Locations
Australia, New South Wales
St Vincent's Hospital
Sydney, New South Wales, Australia, 2010
Australia, Victoria
The Alfred Hospital
Prahran, Victoria, Australia, 3181
Sponsors and Collaborators
St Vincent's Hospital, Sydney
ViiV Healthcare
Investigators
Principal Investigator: Bruce J Brew, MBBS, PhD St Vincent's Hospital, Sydney
  More Information

Responsible Party: Bruce Brew, Professor, St Vincent's Hospital, Sydney
ClinicalTrials.gov Identifier: NCT01434654     History of Changes
Other Study ID Numbers: 09/192  COL114560 
Study First Received: September 12, 2011
Results First Received: February 9, 2016
Last Updated: July 6, 2016
Health Authority: Australia: Human Research Ethics Committee

Keywords provided by St Vincent's Hospital, Sydney:
HAND
HIV
Neurology
Neurocognitive
Neuro-HAART
HIV Associated Neurocognitive Disorders (HAND)

ClinicalTrials.gov processed this record on August 24, 2016