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

St Vincent's Hospital, Sydney

Status: Terminated

Conditions: HIV

Study type: Observational

Funder types: Other; Industry

Identifiers

NCT01434654

09/192

COL114560 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Enrollment: 19 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

19 participants in 2 patient groups

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.

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.