HIV Neuropathy—a Review of Mechanisms, Diagnosis, and Treatment of Pain

Egan, Kaitlyn E.; Caldwell, Gregory M.; Eckmann, Maxim

doi:10.1007/s11916-021-00971-2

Cited by 7 publications

(8 citation statements)

References 25 publications

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“…It is associated with a lower quality of life [ 10 ], can affect productivity, reduces the likelihood of employment, and is associated with substantial financial costs [ 14 , 19 , 20 ]. The proportion of patients reporting peripheral neuropathy (22.4%) in this study according to the criteria of the ACTG-BPNST was comparable to that of previous studies [ 11 ]. In a systematic review by Ghosh et al, it was estimated that peripheral neuropathy amongst ART-exposed patients occurs in the range of 20.3–66% [ 14 ].…”

Section: Discussionsupporting

confidence: 88%

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

Schuldt,

Bern,

Hart

et al. 2023

Viruses

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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.

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Section: Discussionsupporting

confidence: 88%

“…Furthermore, irrespective of its cause, peripheral neuropathy has been found to be associated with a lower quality of life [ 10 ], which highlights the necessity for HIV neuropathy management [ 11 ]. However, effective management strategies, particularly for painful HIV peripheral neuropathy, remain mostly an unmet need.…”

Section: Introductionmentioning

confidence: 99%

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

Schuldt,

Bern,

Hart

et al. 2023

Viruses

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“…This occurs in 20% to 60% of patients and affects both small and large sensory fibers, with prominent loss of small unmyelinated fibers (CASE 6-1). 34 Clinical symptoms of HIV distal sensory polyneuropathy include painful paresthesia and numbness affecting the extremities in a length-dependent distal symmetric distribution. Some patients are asymptomatic, however, and the neuropathy is identified only on examination.…”

Section: Human Immunodeficiency Virusmentioning

confidence: 99%

“…The most common peripheral nervous system disorder in HIV is distal sensory polyneuropathy. This occurs in 20% to 60% of patients and affects both small and large sensory fibers, with prominent loss of small unmyelinated fibers ( case 6-1 ) 34 …”

Section: Viral Infectionsmentioning

confidence: 99%

Infectious Neuropathies

Boegle,

Narayanaswami

2023

CONTINUUM: Lifelong Learning in Neurology

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Objective This article discusses the clinical manifestations and management of infectious peripheral neuropathies. Latest Developments Several infectious etiologies of peripheral neuropathy are well-recognized and their treatments are firmly established. The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with several central and peripheral nervous system manifestations, including peripheral neuropathies. Additionally, some COVID-19 vaccines have been associated with Guillain-Barré syndrome. These disorders are an active area of surveillance and research. Recent evidence-based guidelines have provided updated recommendations for the diagnosis and treatment of Lyme disease. Essential Points Infectious agents of many types (primarily bacteria and viruses) can affect the peripheral nerves, resulting in various clinical syndromes such as mononeuropathy or mononeuropathy multiplex, distal symmetric polyneuropathy, radiculopathy, inflammatory demyelinating polyradiculoneuropathy, and motor neuronopathy. Knowledge of these infections and the spectrum of peripheral nervous system disorders associated with them is essential because many have curative treatments. Furthermore, understanding the neuropathic presentations of these disorders may assist in diagnosing the underlying infection.

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“…Thermal and mechanical hypersensitivity are also prominent symptoms in the peripheral neuropathy developed after chemotherapeutic treatments for cancer (i.e., platinum-derived drugs, vinca alkaloids and taxanes) [ 14 ] or viral infections (HIV, HCV, HSV, HZV) [ 15 , 16 ]. Some channels of the TRP family expressed in nociceptors, like TRPV1, TRPV4, TRPA1 and TRPM8 seem to contribute to this painful, exacerbated sensitivity [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

β–Lactam TRPM8 Antagonist RGM8-51 Displays Antinociceptive Activity in Different Animal Models

Martín-Escura

Medina-Peris

Spear

et al. 2022

IJMS

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Transient receptor potential melastatin subtype 8 (TRPM8) is a cation channel extensively expressed in sensory neurons and implicated in different painful states. However, the effectiveness of TRPM8 modulators for pain relief is still a matter of discussion, since structurally diverse modulators lead to different results, depending on the animal pain model. In this work, we described the antinociceptive activity of a β–lactam derivative, RGM8-51, showing good TRPM8 antagonist activity, and selectivity against related thermoTRP channels and other pain-mediating receptors. In primary cultures of rat dorsal root ganglion (DRG) neurons, RGM8-51 potently reduced menthol-evoked neuronal firing without affecting the major ion conductances responsible for action potential generation. This compound has in vivo antinociceptive activity in response to cold, in a mouse model of oxaliplatin-induced peripheral neuropathy. In addition, it reduces cold, mechanical and heat hypersensitivity in a rat model of neuropathic pain arising after chronic constriction of the sciatic nerve. Furthermore, RGM8-51 exhibits mechanical hypersensitivity-relieving activity, in a mouse model of NTG-induced hyperesthesia. Taken together, these preclinical results substantiate that this TRPM8 antagonist is a promising pharmacological tool to study TRPM8-related diseases.

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HIV Neuropathy—a Review of Mechanisms, Diagnosis, and Treatment of Pain

Cited by 7 publications

References 25 publications

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

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

Infectious Neuropathies

β–Lactam TRPM8 Antagonist RGM8-51 Displays Antinociceptive Activity in Different Animal Models

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