A Follow up Study Evaluating the Effects of HIV Related Cognitive Impairment
Citation:Zaporojan, Lilia, A Follow up Study Evaluating the Effects of HIV Related Cognitive Impairment, Trinity College Dublin.School of Medicine, 2020
Study background: The introduction and availability of highly active antiretroviral therapy (HAART) led to an increased life expectancy among people living with HIV (PLWH) and reduced the incidence of HIV associated dementia (HAD). However, milder forms of disease related cognitive impairment (CI), known as HIV associated neurocognitive disorders (HAND) remain frequent and validation of biomarkers of the disease course and prognosis is needed. This project involved follow-up studies of an Irish cohort of PLWH who were screened for HIV related CI between 2010 and 2013 (McNamara et al., 2014), to evaluate the changes in the brain associated with HAND assessed by a battery of neuropsychological tests and different neuroimaging techniques. Hypothesis: This work is centred on the hypothesis that HIV virus enters the central nervous system (CNS) with infected immune cells (macrophages) causing early inflammation evolving later into a neurodegenerative process from apoptosis and other programmed cell death mechanisms. This model would predict a slow steady cognitive and functional decline in patients with HIV. Aims: The primary aim of this study was to evaluate the natural course of HAND in the era of HAART by following an already well characterised cohort of PLWH with the use of a neuropsychology test battery and multimodal neuroimaging (MRI) data analysis. Additional sub-aims were to evaluate whether or not PLWH who also suffer from HIV related CI use hospital resources more intensively, and whether or not PLWH have a higher burden of other neurological conditions, such as seizures and epilepsy. Methods: A sub-cohort of 79 HIV+ patients who attend HIV services at St. James's Hospital (SJH) and who screened positive for CI and underwent detailed baseline assessments (McNamara et al., 2014) were followed between November 2014 and December 2016, with clinical, functional and a range of neuropsychological examinations (RBANS, ACE-r, MoCA, FAB) to evaluate for presumed cognitive function decline. To assess for progressive grey and white matter alteration at follow-up, a multimodal neuroimaging approach involving Volumetric Brain Morphometry (VBM) and Diffusion Tensor Imaging (DTI) was used in a subset of 42 HIV+ patients who also underwent neuroimaging data acquisition at baseline. To compare hospital services utilisation and costs in PLWH with and without CI, clinical and financial data was obtained from the SJH hospital's Patient Administration System (PAS), hospital electronic patient records (EPR) system, and financial department on a randomly selected subgroup of 200 of the original 604 participants screened for CI. The burden of seizures and epilepsy in the original cohort of 604 subjects was evaluated using the healthcare records (HCR) and EPR. Results: On neuropsychological follow-up, this cohort showed overall stability with only a minority of PLWH progressing to severe cognitive impairment. MRI showed marked widespread inflammatory / microstructural changes in the white matter at baseline with relative stability at follow-up. Indolent, however statistically not significant, cortical grey matter loss was also observed over time. PLWH who screened positive for CI were shown to have poorer clinical outcomes and to use hospital resources more intensively than those screening negative. Lastly, PLWH were found to have a higher burden of seizures than the seronegative population. They often fail to achieve seizure control and disengage from specialist services. Conclusions: The main conclusion of this study is that no substantial decline was found between the two time points on neuropsychology assessments and this was reinforced by the follow-up MRI results suggesting that HAART treatment stabilises the disease and possibly the HIV related CI in the majority of the treated patients. Despite its limitations, this research further supports current clinical guidelines advising early treatment initiation to achieve HIV disease stability for all PLWH. It also underpins the importance of promoting social and community supports that enable engagement with HIV services, which facilitates treatment adherence.
Lundbeck Bursary Award
Author: Zaporojan, Lilia
Publisher:Trinity College Dublin. School of Medicine. Discipline of Clinical Medicine
Type of material:Thesis
Availability:Full text available