HIV-related neuropathy: current perspectives

Abstract

Distal symmetric polyneuropathy (DSP) related to human immunodeficiency virus (HIV) is one of the most common neurologic complications of HIV, possibly affecting as many as 50% of all individuals infected with HIV. Two potentially neurotoxic mechanisms have been proposed to play a crucial role in the pathogenesis of HIV DSP: neurotoxicity resulting from the virus and its products; as well as adverse neurotoxic effects of medications used in the treatment of HIV. Clinically, HIV DSP is characterized by a combination of signs and symptoms that include decreased deep tendon reflexes at the ankles and decreased sensation in the distal extremities as well as paresthesias, dysesthesias, and pain in a symmetric stocking–glove distribution. These symptoms are generally static or slowly progressive over time, and depending on the severity, may interfere significantly with the patient’s daily activities. In addition to the clinical picture, nerve conduction studies and skin biopsies are often pursued to support the diagnosis of HIV DSP. Anticonvulsants, antidepressants, topical agents, and nonspecific analgesics may help relieve neuropathic pain. Specifically, gabapentin, lamotrigine, pregabalin, amitriptyline, duloxetine, and high-dose topical capsaicin patches have been used in research and clinical practice. Further research is needed to elucidate the pathogenesis of HIV DSP, thus facilitating the development of novel treatment strategies. This review discusses the epidemiology, pathophysiology, clinical findings, diagnosis, and management of DSP in the setting of HIV.

Racial and socioeconomic disparities in the symptom reporting of persons living with HIV

“…The lower incidence of neuropathy in our study sample may be contributed to improvements in ART, as many of those studies are dated. It may also be a result of selection bias in some of the smaller studies that focus only on PLWH with neuropathy symptoms, since people report a high burden associated with this symptom and therefore may be more likely to seek help and participate in studies related to their symptom burden(68–70). …”

P2Y12 receptor upregulation in satellite glial cells is involved in neuropathic pain induced by HIV glycoprotein 120 and 2′,3′-dideoxycytidine

“…Distal symmetric polyneuropathy has been recognized as one of the most common neurologic complications of HIV [1][2][3]. The direct neurotoxicity of HIV and the neurotoxic effects of combination antiretroviral therapy medications are both thought to contribute to the development of HIV distal symmetric polyneuropathy [1][2][3]. Glycoprotein 120 (gp120) is involved in the indirect neurotoxic effects of HIV on the peripheral nervous system [2,[4][5][6].…”

“…Glycoprotein 120 (gp120) is involved in the indirect neurotoxic effects of HIV on the peripheral nervous system [2,[4][5][6]. As one type of neurotoxic combination antiretroviral therapy drugs, nucleoside analog reversetranscriptase inhibitors have been shown to be associated with distal symmetric polyneuropathy [1,3,7]. HIVand nucleoside analog reverse-transcriptase inhibitors have synergistic neurotoxic effects.…”

Distal leg epidermal nerve fiber density as a surrogate marker of HIV-associated sensory neuropathy risk: risk factors and change following initial antiretroviral therapy

“…Despite differences in definition and methodology, rates of HIV SN in ranges as high as 50–60 % have been reported in the literature particularly with use of d4T as part of the ART regimens (Schutz and Robinson-Papp 2013 ). Very few subjects in our study developed neuropathic signs or symptoms on this study even in the arm utilizing d4T.…”