Efficacy of Neuro-HAART in Patients With HIV

NCT01434654 | Terminated Results

• 2 other identifiers: 09/192COL114560
• Study Type: observational
• Target: 19
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

HIV

Keywords

HAND; HIV; Neurology; Neurocognitive; Neuro-HAART; HIV Associated Neurocognitive Disorders (HAND)

Outcome Measures

Primary Outcomes (1)

• Change in Neurocognitive Functioning

  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.

  Change from baseline Neuropsychological testing at 6 and 12 months

Secondary Outcomes (3)

• Change in MRS Cerebral Metabolite Ratios in Basal Ganglia

  Baseline and 12 months

• Change in MRS Cerebral Metabolite Ratios in Frontal White Matter

  Baseline and 12 months

• Cerebrospinal Fluid

  Baseline to 12 Months

Study Arms (2)

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 Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

HIV positive participants on HAART who attend outpatient primary care clinics.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• St Vincent's Hospital, Sydney: lead
• ViiV Healthcare: collaborator

Study Sites (2)

St Vincent's Hospital

Sydney, New South Wales, 2010, Australia

Location

The Alfred Hospital

Prahran, Victoria, 3181, Australia

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Cerbrospinal fluid and bloods

Limitations and Caveats

Lower than expected participant recruitment rate and early termination led to a small sample size and underpowered statistical analyses

Results Point of Contact

• Title: Prof. Bruce Brew
• Organization: St Vincent's Hospital, Sydney

b.brew@unsw.edu.au

+61 2 8382 1111

Study Officials

• Bruce J Brew, MBBS, PhD

  St Vincent's Hospital, Sydney

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 12, 2011
• First Posted: September 15, 2011
• Study Start: September 1, 2011
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: August 9, 2016
• Results First Posted: May 20, 2016

Record last verified: 2016-07

Locations

AU (2)