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Title: A clinical investigation of chronic pain in subjects with HIV-associated sensory neuropathy
Author: Kemp, Harriet
ISNI:       0000 0004 7658 900X
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2019
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HIV-associated sensory neuropathy (HIV-SN) is a debilitating complication of HIV infection and its treatment. However, no commercially available pharmacotherapy has demonstrated consistent efficacy at clinical trial. This study aims to identify strategies to improve clinical trial design in HIV-SN by deeply phenotyping a cohort of people living with HIV, and through a meta-analysis of the placebo response in HIV-SN trials. 148 subjects were recruited, including 81 with HIV-SN. Age was the only independent predictor of neuropathy in this cohort. The prevalence of multiple chronic pain diagnoses was high, especially in those with HIV-SN (82.5% versus 61.2%, p=0.0008). This indicates that careful characterisation of painful conditions at trial entry is required to identify efficacy of the intervention with respect to HIV-SN-related symptoms specifically. Subjects showed heterogeneity of symptoms and signs, determined by symptom-based questionnaires and quantitative sensory testing, and could be allocated to distinct 'sensory profiles'. Those with HIV-SN displayed predominantly 'mechanical hyperalgesia' (43.2%) and 'sensory loss' (30.3%) profiles. Similar profiling at clinical trial enrolment could allow for the identification of differential responses to therapy at a sub-group level. A preliminary healthy volunteer study allowed for assessment of reliability and measurement error in conditioned pain modulation (CPM). There was no difference in CPM response between those with and without neuropathy, but the response was heterogeneous. CPM may not yet be robust enough to recommend as a profiling measure in trials of HIV-SN. Corneal confocal microscopy and a point-of-care nerve conduction device were assessed for their effectiveness as tools for screening and monitoring HIV-SN. Both were shown to be useful and have the potential to increase the certainty of a diagnosis of neuropathic pain at trial enrolment. A 2012 meta-analysis identified a greater placebo response in trials of HIV-SN compared to other neuropathic pain conditions. Repeat meta-analysis identified no difference in placebo response between HIV-SN and a comparable sensory neuropathy, diabetic polyneuropathy.
Supervisor: Rice, Andrew Sponsor: European Commission
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral