Efficacy of Neuro-HAART in Patients With HIV

HIV Clinical Trial

— HANDobs  

Official title:

The Efficacy of Neuro-HAART in HIV Infected Individuals

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01434654
• Other study ID #: 09/192
• Secondary ID: COL114560
• Status: Not yet recruiting
• Phase: N/A
• First received: September 12, 2011
• Last updated: October 7, 2012
• Start date: September 2011

Study information

• Verified date: October 2012
• Source: St Vincent's Hospital, Sydney
• Contact: Bruce J Brew, MBBS, PhD
• Phone: 61 2 8382 1111
• Email: bbrew[@]stvincents.com.au
• Is FDA regulated: No
• Health authority: Australia: Human Research Ethics Committee
• Study type: Observational

Clinical Trial 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. At study initiation a lumbar puncture would be performed so that drugs levels could be measured in CSF.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 170
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• HIV positive with nadir CD4 count <350 /uL

• Taking HAART with CNS Penetration Effectiveness (CPE) score of either =7.0 or =7.5 for 1 year or more. Changes in 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, 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 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

Study Design

Time Perspective: Prospective

Related Conditions & MeSH terms

• HIV

Locations

Country	Name	City	State
Australia	The Alfred Hospital	Prahran	Victoria
Australia	St Vincent's Hospital	Sydney	New South Wales

Sponsors (2)

Lead Sponsor	Collaborator
St Vincent's Hospital, Sydney	ViiV Healthcare

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Neurocognitive Function	To compare the change in summary neuropsychological 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.	Change from baseline Neuropsychological testing, at 12 months	No
Secondary	Magnetic Resonance Imaging (MRI - Brain)	To compare the change in brain magnetic resonance spectroscopy in predefined regions of interest, after a 12-month period of observation, between HIV positive patients taking antiretroviral regimens categorized as being either of high or low CNS penetration.	Change from baseline MRI, at 12 months	No
Secondary	Cerebrospinal Fluid	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); and will be correlated with the neuropsychological and MR spectroscopy outcome measures. Additionally, to ascertain whether pharmacokinetic interactions between ARVs affect CSF levels of the individual drugs.	Change in CNS penetrance of ARV medications from baseline to 12 months	No