The Efficacy of Neuro-HAART in HIV Infected Individuals

Efficacy of Neuro-HAART in Patients With HIV

Sponsors

Lead sponsor: St Vincent's Hospital, Sydney

Collaborator: ViiV Healthcare

Source St Vincent's Hospital, Sydney
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.

Overall Status Terminated
Start Date September 2011
Completion Date September 2014
Primary Completion Date September 2014
Study Type Observational
Primary Outcome
Measure Time Frame
Change in Neurocognitive Functioning Change from baseline Neuropsychological testing at 6 and 12 months
Secondary Outcome
Measure Time Frame
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
Enrollment 19
Condition
Eligibility

Sampling method: Non-Probability Sample

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

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Bruce J Brew, MBBS, PhD Principal Investigator St Vincent's Hospital, Sydney
Location
facility
St Vincent's Hospital | Sydney, New South Wales, 2010, Australia
The Alfred Hospital | Prahran, Victoria, 3181, Australia
Location Countries

Australia

Verification Date

July 2016

Responsible Party

Responsible party type: Principal Investigator

Investigator affiliation: St Vincent's Hospital, Sydney

Investigator full name: Bruce Brew

Investigator title: Professor

Keywords
Has Expanded Access No
Arm Group

Arm group label: Non Neuro-HAART (low CNS penetrance)

Description: 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.

Arm group label: Neuro-HAART (high CNS penetrance)

Description: 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.

Acronym HANDobs
Study Design Info

Observational model: Cohort

Time perspective: Prospective

Source: ClinicalTrials.gov