{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T13:42:47Z","timestamp":1792590167086,"version":"4.5.0"},"reference-count":42,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,19]],"date-time":"2023-12-19T00:00:00Z","timestamp":1702944000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute for Health Research Health Technology Assessment"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The aim of this study is to identify the factors associated with peripheral neuropathy and to explore neurofilament light chain (NfL) as a biomarker for peripheral neuropathy (PN) in effectively virologically suppressed adults living with HIV. All protease inhibitor monotherapy versus ongoing triple therapy in the long-term management of HIV infection (PIVOT) trial participants with data on PN at baseline were included in the study. NfL plasma levels (pNfL) were measured in a sub-set of participants. Multivariable logistic regression was used to examine the associations of PN with potential risk factors (including age, sex, nadir CD4 cell count, history of dideoxynucleoside (d-drugs) exposure, and blood glucose levels) and NfL levels. Of the 585 participants included, 131 (22.4%) reported PN during the study period (median of 44 months). The participants were predominantly male (76.6%), White (68.2%), and virologically suppressed for a median period of 37 months (range of 20\u201363) before recruitment. The age at baseline was 44.3 years (standard deviation (SD) of 9.2). PN was independently associated with age (adjusted odds ratio (aOR) = 1.35, 95% CI of 1.20\u20131.52; additional 5 years), history of d-drugs (aOR 1.88, 95% CI of 1.12\u20133.16), height (aOR 1.19, 95% CI of 1.05\u20131.35; additional 5 cm), nadir CD4 cell count (aOR 1.10 CI of 1.00\u20131.20; 50 cells fewer), and metabolic syndrome (aOR 2.31, 95% CI of 1.27 4.20), but not pNfL. The excess risk for PN associated with d-drug use remains after the exposure has stopped for years, suggesting non-reversible toxicity. In people with HIV, metabolic syndrome is independently associated with PN. There was no additional value for pNfL as a screening test for peripheral neuropathy in effectively virologically suppressed adults living with HIV.<\/jats:p>","DOI":"10.3390\/v16010002","type":"journal-article","created":{"date-parts":[[2023,12,19]],"date-time":"2023-12-19T04:18:37Z","timestamp":1702959517000},"page":"2","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Peripheral Neuropathy in Virologically Suppressed People Living with HIV: Evidence from the PIVOT Trial"],"prefix":"10.3390","volume":"16","author":[{"given":"Anna L.","family":"Schuldt","sequence":"first","affiliation":[{"name":"Institute for Global Health, University College London, London WC1E 6JB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Bern","sequence":"additional","affiliation":[{"name":"MRC Clinical Trials Unit at UCL, University College London, London WC1V 6LJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Hart","sequence":"additional","affiliation":[{"name":"Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Gompels","sequence":"additional","affiliation":[{"name":"Service of Immunology, Southmead Hospital, Bristol BS10 5NB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Winston","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Imperial College London, London SW7 2BX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Clarke","sequence":"additional","affiliation":[{"name":"Department of HIV, Sexual Health and Contraception, Brighton and Sussex University Hospitals NHS Trust, Brighton BN11 2DH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"Chen","sequence":"additional","affiliation":[{"name":"Florey Unit Clinic for Sexual Health, Royal Berkshire Hospital, Reading RG1 5AN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"St\u00f6hr","sequence":"additional","affiliation":[{"name":"MRC Clinical Trials Unit at UCL, University College London, London WC1V 6LJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Heslegrave","sequence":"additional","affiliation":[{"name":"Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas I.","family":"Paton","sequence":"additional","affiliation":[{"name":"MRC Clinical Trials Unit at UCL, University College London, London WC1V 6LJ, UK"},{"name":"Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0344-9749","authenticated-orcid":false,"given":"Axel","family":"Petzold","sequence":"additional","affiliation":[{"name":"Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Arenas-Pinto","sequence":"additional","affiliation":[{"name":"Institute for Global Health, University College London, London WC1E 6JB, UK"},{"name":"MRC Clinical Trials Unit at UCL, University College London, London WC1V 6LJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1055\/s-0038-1649334","article-title":"Global Health Neurology: HIV\/AIDS","volume":"38","author":"Patel","year":"2018","journal-title":"Semin. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1111\/ene.14656","article-title":"Human immunodeficiency virus-related peripheral neuropathy: A systematic review and meta-analysis","volume":"28","author":"Julian","year":"2021","journal-title":"Eur. J. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/S1474-4422(13)70002-4","article-title":"Manifestations of HIV infection in the peripheral nervous system","volume":"12","author":"Centner","year":"2013","journal-title":"Lancet Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1097\/00002030-200305020-00024","article-title":"Lactate concentrations distinguish between nucleoside neuropathy and HIV neuropathy","volume":"17","author":"Brew","year":"2003","journal-title":"Aids"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1097\/01.aids.0000180786.02930.a1","article-title":"Mitochondrial haplogroups and peripheral neuropathy during antiretroviral therapy: An adult AIDS clinical trials group study","volume":"19","author":"Hulgan","year":"2005","journal-title":"Aids"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1007\/s13365-013-0216-4","article-title":"Peripheral neuropathy in ART-experienced patients: Prevalence and risk factors","volume":"19","author":"Chen","year":"2013","journal-title":"J. Neurovirol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.beem.2011.04.003","article-title":"The prevalence and pathogenesis of diabetes mellitus in treated HIV-infection","volume":"25","author":"Paik","year":"2011","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"136","DOI":"10.2337\/dc16-2042","article-title":"Diabetic neuropathy: A position statement by the American Diabetes Association","volume":"40","author":"Boulton","year":"2017","journal-title":"Diabetes Care"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1007\/s13365-015-0374-7","article-title":"Peripheral neuropathy in HIV patients in sub-Saharan Africa failing first-line therapy and the response to second-line ART in the EARNEST trial","volume":"22","author":"Thompson","year":"2016","journal-title":"J. Neurovirol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1017\/S0317167100003978","article-title":"HIV-related neurological syndromes reduce health-related quality of life","volume":"32","author":"Pandya","year":"2005","journal-title":"Can. J. Neurol. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/s11916-021-00971-2","article-title":"HIV Neuropathy-a Review of Mechanisms, Diagnosis, and Treatment of Pain","volume":"25","author":"Egan","year":"2021","journal-title":"Curr. Pain. Headache Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e417","DOI":"10.1016\/S2352-3018(15)00176-9","article-title":"Protease inhibitor monotherapy for long-term management of HIV infection: A randomised, controlled, open-label, non-inferiority trial","volume":"2","author":"Paton","year":"2015","journal-title":"Lancet HIV"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1212\/01.wnl.0000187119.33075.41","article-title":"Evaluation of a clinical screening tool for HIV-associated sensory neuropathies","volume":"65","author":"Cherry","year":"2005","journal-title":"Neurology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1089\/aid.2011.0116","article-title":"Epidemiology of HIV-related neuropathy: A systematic literature review","volume":"28","author":"Ghosh","year":"2012","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1212\/01.wnl.0000218303.48113.5d","article-title":"HIV neuropathy natural history cohort study: Assessment measures and risk factors","volume":"66","author":"Simpson","year":"2006","journal-title":"Neurology"},{"key":"ref_16","unstructured":"International Diabetes Federation (IDF) (2022, June 30). Metabolic Syndrome: The IDF Consensus Worldwide Definition of Metabolic Syndrome [Online]. Available online: https:\/\/idf.org\/about-diabetes\/resources\/."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1093\/cid\/ciw279","article-title":"Neurocognitive Function and Neuroimaging Markers in Virologically Suppressed HIV-positive Patients Randomized to Ritonavir-boosted Protease Inhibitor Monotherapy or Standard Combination ART: A Cross-sectional Substudy From the PIVOT Trial","volume":"63","author":"Haddow","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"116451","DOI":"10.1016\/j.jns.2019.116451","article-title":"Peripheral neuropathy in HIV patients on antiretroviral therapy: Does it impact function?","volume":"406","author":"Dudley","year":"2019","journal-title":"J. Neurol. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s13098-015-0010-y","article-title":"Peripheral neuropathy is associated with insulin resistance independent of metabolic syndrome","volume":"7","author":"Han","year":"2015","journal-title":"Diabetol. Metab. Syndr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1136\/jnnp-2016-314171","article-title":"Metabolic syndrome is related to polyneuropathy and impaired peripheral nerve function: A prospective population-based cohort study","volume":"87","author":"Hanewinckel","year":"2016","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1111\/1753-0407.13075","article-title":"Associations between general and abdominal obesity and incident diabetic neuropathy in participants with type 2 diabetes mellitus","volume":"13","author":"Zhou","year":"2021","journal-title":"J. Diabetes"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1016\/j.mayocp.2020.03.025","article-title":"Central Obesity is Associated With Neuropathy in the Severely Obese","volume":"95","author":"Callaghan","year":"2020","journal-title":"Mayo Clin. Proc."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"949315","DOI":"10.3389\/fnut.2022.949315","article-title":"Comparison of waist-height ratio and other obesity indices in the prediction of diabetic peripheral neuropathy","volume":"9","author":"Lawal","year":"2022","journal-title":"Front. Nutr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1002\/acn3.51097","article-title":"Predictors of worsening neuropathy and neuropathic pain after 12 years in people with HIV","volume":"7","author":"Ellis","year":"2020","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2317","DOI":"10.1097\/QAD.0b013e328332204e","article-title":"Role of metabolic syndrome components in HIV associated sensory neuropathy","volume":"23","author":"Ances","year":"2009","journal-title":"Aids"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.jchemneu.2016.04.006","article-title":"Axonopathy in peripheral neuropathies: Mechanisms and therapeutic approaches for regeneration","volume":"76","author":"Landowski","year":"2016","journal-title":"J. Chem. Neuroanat."},{"key":"ref_27","unstructured":"Ellis, R., Rosario, D., Clifford, D., McArthur, J., Simpson, D., Alexander, T., Marra, C., Gelman, B.B., and Grant, I. (2009, January 8\u201311). Persisting high prevalence of HIV distal sensory peripheral neuropathy in the era of combination ART: Correlates in the CHARTER study; [Poster #461]. Proceedings of the 16th Conference on Retroviruses and Opportunistic Infections, Montreal, QC, Canada."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2579","DOI":"10.1097\/QAD.0000000000000447","article-title":"Prevalence, incidence and predictors of peripheral neuropathy in African adults with HIV infection within the DART trial","volume":"28","author":"Kikaire","year":"2014","journal-title":"Aids"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1212\/01.wnl.0000203336.12114.09","article-title":"Antiretroviral use and other risks for HIV-associated neuropathies in an international cohort","volume":"66","author":"Cherry","year":"2006","journal-title":"Neurology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1007\/s11764-021-00988-x","article-title":"Metabolic and lifestyle risk factors for chemotherapy-induced peripheral neuropathy in taxane and platinum-treated patients: A systematic review","volume":"17","author":"Timmins","year":"2023","journal-title":"J. Cancer Surviv."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1097\/QAD.0b013e328345889d","article-title":"Peripheral neuropathy in HIV: Prevalence and risk factors","volume":"25","author":"Evans","year":"2011","journal-title":"Aids"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Moketla, M.B., Wadley, A.L., Kamerman, P., and de Assis Rosa, D. (2018). Pharmacogenetic variation influences sensory neuropathy occurrence in Southern Africans treated with stavudine-containing antiretroviral therapy. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0204111"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1016\/j.jpainsymman.2010.07.006","article-title":"HIV Neuropathy Risk Factors and Symptom Characterization in Stavudine-Exposed South Africans","volume":"41","author":"Wadley","year":"2011","journal-title":"J. Pain. Symptom Manag."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1002\/ana.22150","article-title":"Mitochondrial dysfunction in distal axons contributes to human immunodeficiency virus sensory neuropathy","volume":"69","author":"Lehmann","year":"2011","journal-title":"Ann. Neurol."},{"key":"ref_35","first-page":"303","article-title":"Peripheral neuropathy in primary HIV infection associates with systemic and central nervous system immune activation","volume":"66","author":"Wang","year":"2014","journal-title":"Am. J. Ther."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1001\/archneur.61.4.546","article-title":"HIV-Associated Distal Sensory Polyneuropathy in the Era of Highly Active Antiretroviral Therapy: The Manhattan HIV Brain Bank","volume":"61","author":"Morgello","year":"2004","journal-title":"Arch. Neurol-Chicago"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"727311","DOI":"10.3389\/fnins.2021.727311","article-title":"Magnetic Resonance Imaging as a Biomarker in Diabetic and HIV-Associated Peripheral Neuropathy: A Systematic Review-Based Narrative","volume":"15","author":"Evans","year":"2021","journal-title":"Front. Neurosci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/s41582-018-0058-z","article-title":"Neurofilaments as biomarkers in neurological disorders","volume":"14","author":"Khalil","year":"2018","journal-title":"Nat. Rev. Neurol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1111\/jnc.15682","article-title":"The 2022 Lady Estelle Wolfson lectureship on neurofilaments","volume":"163","author":"Petzold","year":"2022","journal-title":"J. Neurochem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.ebiom.2015.11.036","article-title":"Plasma Concentration of the Neurofilament Light Protein (NFL) is a Biomarker of CNS Injury in HIV Infection: A Cross-Sectional Study","volume":"3","author":"Price","year":"2016","journal-title":"EBioMedicine"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"P4.9-005","DOI":"10.1212\/WNL.92.15_supplement.P4.9-005","article-title":"Neurofilament Light Chain Protein Levels in HIV Positive Subjects with Neuropathy (P4.9-005)","volume":"92","author":"Damian","year":"2019","journal-title":"Neurology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1007\/s13365-021-01026-3","article-title":"Correlation between cerebrospinal fluid and plasma neurofilament light protein in treated HIV infection: Results from the COBRA study","volume":"28","author":"Alagaratnam","year":"2022","journal-title":"J. Neurovirol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/1\/2\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:41:15Z","timestamp":1760132475000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/1\/2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,19]]},"references-count":42,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["v16010002"],"URL":"https:\/\/doi.org\/10.3390\/v16010002","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,19]]}}}