title: Development, Validation, and Field-Testing of an Instrument for Clinical Assessment of HIV-Associated Neuropathy and Neuropathic Pain in Resource-Restricted and Large Population Study Settings.
abstract: HIV-associated sensory peripheral neuropathy (HIV-SN) afflicts approximately 50% of patients on antiretroviral therapy, and is associated with significant neuropathic pain. Simple accurate diagnostic instruments are required for clinical research and daily practice in both high- and low-resource setting. A 4-item clinical tool (CHANT: Clinical HIV-associated Neuropathy Tool) assessing symptoms (pain and numbness) and signs (ankle reflexes and vibration sense) was developed by selecting and combining the most accurate measurands from a deep phenotyping study of HIV positive people (Pain In Neuropathy Study-HIV-PINS). CHANT was alpha-tested in silico against the HIV-PINS dataset and then clinically validated and field-tested in HIV-positive cohorts in London, UK and Johannesburg, South Africa. The Utah Early Neuropathy Score (UENS) was used as the reference standard in both settings. In a second step, neuropathic pain in the presence of HIV-SN was assessed using the Douleur Neuropathique en 4 Questions (DN4)-interview and a body map. CHANT achieved high accuracy on alpha-testing with sensitivity and specificity of 82% and 90%, respectively. In 30 patients in London, CHANT diagnosed 43.3% (13/30) HIV-SN (66.7% with neuropathic pain); sensitivity = 100%, specificity = 85%, and likelihood ratio = 6.7 versus UENS, internal consistency = 0.88 (Cronbach alpha), average item-total correlation = 0.73 (Spearman's Rho), and inter-tester concordance > 0.93 (Spearman's Rho). In 50 patients in Johannesburg, CHANT diagnosed 66% (33/50) HIV-SN (78.8% neuropathic pain); sensitivity = 74.4%, specificity = 85.7%, and likelihood ratio = 5.29 versus UENS. A positive CHANT score markedly increased of pre- to post-test clinical certainty of HIV-SN from 43% to 83% in London, and from 66% to 92% in Johannesburg. In conclusion, a combination of four easily and quickly assessed clinical items can be used to accurately diagnose HIV-SN. DN4-interview used in the context of bilateral feet pain can be used to identify those with neuropathic pain.
authors.affiliation: Pain Research, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom.|Department of Neurology, Addis Abäba University School of Medicine, College of Health Sciences, Addis Abäba, Ethiopia.|Advanced Clinical Consultation & Research Center, Addis Abäba, Ethiopia.
authors.forename: Yohannes W
authors.identifier: http://orcid.org/0000-0003-4879-6098
authors.initials: YW
authors.lastname: Woldeamanuel
authors.affiliation: Brain Function Research Group, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Kamerman
authors.affiliation: Division of Neurology, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Demetri G A
authors.initials: DG
authors.lastname: Veliotes
authors.affiliation: Pain Research, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom.|The Pain Relief Unit, The Churchill Hospital, Oxford, United Kingdom.
authors.forename: Tudor J
authors.initials: TJ
authors.lastname: Phillips
authors.affiliation: The Pain Relief Unit, The Churchill Hospital, Oxford, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Asboe
authors.affiliation: HIV Medicine and Sexual Health, Chelsea and Westminster Hospital, London, United Kingdom.
authors.forename: Marta
authors.initials: M
authors.lastname: Boffito
authors.affiliation: Pain Research, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Andrew S C
authors.initials: AS
authors.lastname: Rice
mesh_terms: D000328:Adult; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006295:Health Resources / Q000600:supply & distribution*; D006801:Humans; D008297:Male; D009437:Neuralgia / Q000150:complications* / Q000175:diagnosis*; D010147:Pain Measurement / Q000191:economics* / Q000379:methods*