The HIV Neurosciences group (Lucette Cysique, Ph.D. & Bruce Brew, MBBS MD FRACP)

Introduction

In 1996, highly active antiretroviral therapy (HAART) started to be widely used to treat HIV-1 infection and effectively lengthened patients’ life expectancy. For patients stable on their medication, HIV infection is now a chronic disease. Despite this success, HIV-associated Neurocognitive Disorders (HAND) has not been eradicated and remains as prevalent as before HAART (up to 50% in advanced HIV+ individuals). This high prevalence might be attributed to HAND cases who initially improved on HAART, and relapsed despite long-term treatment (up to 69% of cases). However for some 21%, this represents new cognitive deficits despite effective HAART. HIV-related neuropathlogical findings in the HAART era are changing. The prevalence of opportunistic infections and CNS neoplasms has decreased, and the frequency and sometimes severity of chronic forms of HIV encephalopathy (HIVE) have been rising as the HAART-treated HIV population ages.

The long-term course of HAND remains poorly understood, especially in the context of chronic HIV infection (i.e., when patients are stable on HAART and for most of the time virally suppressed). In addition, some causes for neurocognitive impairment have changed. Indeed, there is cumulative evidence that in HAART treated patients the current immune status; plasma and CSF viral load do not predict brain dysfunction, while past immune status does. Lastly, there is evidence that some antiretrovirals are better than others at crossing the brain blood barrier and at suppressing HIVRNA more effectively as well as improving cognitive functions. However, the evidence comes from relatively small observational studies and larger randomised studies are necessary.

The HIV and aging research study (Lucette Cysique)

Dr. Lucette Cysique is currently leading the HIV and aging research study at the University of New South Wales, Brain Sciences, based at St. Vincent’s Hospital research campus. The study is currently enrolling chronically HIV-infected individuals aged 45 years+ in a prospective study with cross-disciplinary aims.

The neuropsychological part involves an assessment of cognitive and neuropsychiatric functions as well as emotional processing. Ms Tammy Lane is currently a Neuropsychological Masters student at Macquarie University and her project is dedicated at a better understanding of the interplay between neuropsychological performance, neuropsychiatric symptoms (depression versus apathy) and emotional processing. Ms Tammy Lane is also the study neuropsychological research assistant.

The neuroimaging part of the project is conducted in collaboration with Professor Rae’s research group at Neurosciences Research Australia (http://www.neura.edu.au/research/themes/rae-group). Mr. Jae Myung-Lee is current a Medical Sciences Honors student at UNSW. His project is to determine a MRS and structural MRI profile of chronic HIV-related brain injury on middle-aged individuals.

A PIB PET sub-project is conducted in collaboration with Prof. Rowe, head of the Centre of PET, Austin Health Hospital in Melbourne.

The cardio-vascular part of the project is conducted in collaboration with Prof. Andrew Carr head of the St. Vincent’s Hospital, Immunology Department.

The laboratory analyses are to be conducted in collaboration with Prof. Anthony Kelleher, head of the HIV Immunovirology Lab at St. Vincent’s Centre for Applied Medical Research. For this we are currently looking for a competitive PhD candidate who would be in charge of the laboratory data analysis for a project that aims at searching new biomarkers for HAND.

The genetic part of the project is conducted in collaboration with Prof. Patricia Price at the School of Pathology and Laboratory Medicine University of Western Australia. (http://www.hivimmunology.uwa.edu.au/)

To provide adequate control data, Dr. Cysique is looking for HIV-seronegative healthy individuals also aged 45 years and beyond (see link for more information on HIV-negative study, http://www.acon.org.au/research). The study is supported by UNSW and the NHMRC.

The HIV treatment research studies (Bruce Brew)

Professor Brew is currently leading a worldwide clinical research trial that is expect to open to recruitment in December 2010 to determine whether some antiretrovirals lead to better neurocognitive functions and reduction of CSF viral load faster (“NeuroHAART effect). Dr. Cysique provides neuropsychological expert consultation for this study. A similar study will determine whether intensification of antiretroviral therapy in HAND patients who are virologically suppressed in both blood and CSF improves cognition.

Dr. Lucette Cysique and Professor Brew are both involved as investigators in an international large scaled study which aims is to determine whether early or delayed treatment is associated with worse of better neurological prognostic. (Strategic Timing of AntiRetroviral Treatment (START) study as part of the International Network for Strategic Initiatives in Global HIV Trials (INSIGHT; http://insight.ccbr.umn.edu/start/).