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Title: A clinical investigation of painful HIV-associated sensory neuropathy
Author: Phillips, Tudor
ISNI:       0000 0005 0733 0181
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2014
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HIV-associated sensory polyneuropathy (HIV-SN) is a distal symmetrical polyneuropathy that is a prevalent (approximately 40%), and often painful complication of HIV infection. The introduction of combination antiretroviral treatment (cART), transformed HIV infection from a high mortality condition into a chronic disease. Despite this, and the phasing-out of neurotoxic antiretroviral drugs, HIV-SN continues to be a significant morbidity experienced in HIV infection. Consequently, the understanding, prevention and management of HIV-SN is increasingly important. A systematic review and meta-analysis was undertaken to examine the evidence for the efficacy of pharmacological agents in the management of pain in HIV-SN. Of 44 studies identified, 19 were randomized controlled trials, and only 14 were of sufficient quality. Interventions demonstrating greater efficacy than placebo included smoked cannabis and recombinant nerve growth factor (rhNGF). However rhNGF is not clinically available and smoked cannabis cannot be recommended as routine therapy. A second study was undertaken to phenotype a cohort of HIV infected participants with and without HIV-SN. This study examined demographic factors, symptomatology, metabolic factors, sensory nerve dysfunction through quantitative sensory testing (QST), and intra-epidermal nerve fibre density (IENFD); quality of life, sleep dysfunction and psychological co-morbidity. A novel triumvirate definition using QST, IENFD and a structured neurological examination was used to define HIV-SN. This study showed that patterns of sensory nerve dysfunction are heterogeneous in HIV-SN; the most common feature being loss of sensory function in mechanical and vibration detection modalities. Gain of function sensory changes were infrequent, but were seen in a small sub-group demonstrating wind-up phenomenon; this group demonstrated higher levels of catastrophizing behaviours. Measures of quality of life were generally lower than in other painful peripheral neuropathies. Sleep dysfunction was common in HIV-SN. Participants with HIV-SN had elevated triglycerides (TRG), providing further evidence for the role of dyslipidaemia in HIV-SN pathogenesis.
Supervisor: Rice, Andrew Sponsor: Derek Butler Trust
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral