Clinical trial NCT01434654: Efficacy of Neuro-HAART in Patients With HIV
Official title: The Efficacy of Neuro-HAART in HIV Infected Individuals
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: HIV
Keywords: HAND
HIV
Neurology
Neurocognitive
Neuro-HAART
HIV Associated Neurocognitive Disorders (HAND)
Lead sponsor: St Vincent's Hospital, Sydney
Sponsor class: OTHER
Collaborators: name: ViiV Healthcare
First posted: 2011-09-15
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: HIV positive participants on HAART who attend outpatient primary care clinics.

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.


Eligibility 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

Primary outcomes:
measure: Change in Neurocognitive Functioning
timeFrame: Change from baseline Neuropsychological testing at 6 and 12 months
Secondary outcomes:
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
measure: Cerebrospinal Fluid
timeFrame: Baseline to 12 Months
Other outcomes:
Locations:
city: Sydney
country: Australia
facility: St Vincent's Hospital
state: New South Wales
city: Prahran
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: