Peripheral Neuropathy in Virologically Suppressed People Living with HIV: Evidence from the PIVOT Trial

Author:

Schuldt Anna L.1,Bern Henry2,Hart Melanie3,Gompels Mark4,Winston Alan5,Clarke Amanda6,Chen Fabian7,Stöhr Wolfgang2,Heslegrave Amanda3,Paton Nicholas I.28,Petzold Axel3ORCID,Arenas-Pinto Alejandro12

Affiliation:

1. Institute for Global Health, University College London, London WC1E 6JB, UK

2. MRC Clinical Trials Unit at UCL, University College London, London WC1V 6LJ, UK

3. Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK

4. Service of Immunology, Southmead Hospital, Bristol BS10 5NB, UK

5. Faculty of Medicine, Imperial College London, London SW7 2BX, UK

6. Department of HIV, Sexual Health and Contraception, Brighton and Sussex University Hospitals NHS Trust, Brighton BN11 2DH, UK

7. Florey Unit Clinic for Sexual Health, Royal Berkshire Hospital, Reading RG1 5AN, UK

8. Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore

Abstract

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 20–63) 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 1.20–1.52; additional 5 years), history of d-drugs (aOR 1.88, 95% CI of 1.12–3.16), height (aOR 1.19, 95% CI of 1.05–1.35; additional 5 cm), nadir CD4 cell count (aOR 1.10 CI of 1.00–1.20; 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.

Funder

National Institute for Health Research Health Technology Assessment

Publisher

MDPI AG

Subject

Virology,Infectious Diseases

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