An open-label pilot study of high-concentration capsaicin patch in painful HIV neuropathy.

Peripheral neuropathy is the most frequent neurological complication of human immunodeficiency virus (HIV)-1 infection and is commonly associated with the development of chronic pain. This open-label, 12-week pilot study assessed the efficacy, tolerability, and safety of a high-concentration capsaicin dermal patch (NGX-4010; capsaicin, 640microg/cm2, 8% w/w) to treat painful HIV-associated distal sensory polyneuropathy (DSP). Eligible patients had moderate-to-severe pain in both feet due to HIV-associated DSP or antiretroviral toxic neuropathy. Patients received a single 60-minute application of the investigational high-concentration capsaicin patch to the affected areas. The primary outcome measure was the mean percent change in numeric pain rating scale (NPRS) during weeks two to 12 postadministration. After a single 60-minute NGX-4010 application, the mean percent change from baseline in "average pain for past 24 hours" NPRS scores during weeks two to 12 was -40% (95% CI: -61%, -19%; P=0.0020). Similar results were observed for "worst pain for past 24 hours" and "pain now" scores. Eight of 12 patients (67%) were treatment responders (> or =30% pain decrease). Four of 12 patients (33%) experienced a > or =50% reduction in pain. Treatment was generally well tolerated. Treatment-associated pain was self-limited and could be managed with short-acting opioids. This study demonstrates that treatment of painful HIV-associated neuropathy with a single application of NGX-4010, a high-concentration capsaicin patch, was feasible, well tolerated, and associated with significant reduction in pain over the 12 weeks studied. No safety concerns were identified. Controlled studies of NGX-4010 for the treatment of painful HIV-associated neuropathy are warranted.

Peripheral neuropathies associated with HIV and hepatitis C co-infection: a review.

Co-infection with HIV and hepatitis C has become increasingly prevalent. It is a major source of morbidity in HIV-infected populations. Distal symmetric polyneuropathy is the most common form of peripheral neuropathy in HIV as well as hepatitis C mono-infection. There is considerable overlap in the symptoms and signs of HIV and hepatitis C neuropathy. It is not known whether there are additive or synergistic effects on the peripheral nerve by these two viruses. There is a need for studies to further elucidate the mechanisms involved.

Effects of hepatic function and hepatitis C virus on the nervous system assessment of advanced-stage HIV-infected individuals.

OBJECTIVES: To examine the effects of liver function and hepatitis C virus (HCV) serostatus on neurological, neuropsychological, and psychiatric abnormalities in an advanced-stage HIV-infected cohort. DESIGN: A correlational analysis of baseline data accumulated on 137 participants in the Manhattan HIV Brain Bank, a longitudinal study of HIV-infected individuals. METHODS: Patients underwent a battery of neuropsychological tests, a semi-structured psychiatric interview, and a neurological examination. The resulting diagnostic data were correlated with biochemical indices of hepatic function and HCV serostatus. RESULTS: Biochemical indices of liver function correlated with motor dysfunction determined by neurological evaluation, but not with neuropsychological or psychiatric disorders. Discrete neurological diagnostic entities showed no relationship with biochemical indices, with one exception: patients with cryptococcal leptomeningitis had worse liver function than those without. HCV had no relationship with any neurological disorder or symptom complex. In contrast, HCV serostatus was related to neuropsychological and psychiatric abnormalities, and indices of liver function were not. HCV-seropositive patients were more likely to have histories of opiate, cocaine or stimulant dependency, to have greater impairment in executive functioning, and to meet diagnostic criteria for AIDS dementia, compared with HCV-negative individuals of similar immunological and virological status. CONCLUSIONS: HCV and biochemical indices of liver function associate differentially with nervous system abnormalities in this HIV-infected population. Neurological abnormalities correlate with biochemical indices of liver function, whereas neuropsychological and psychiatric dysfunction are linked to HCV infection. We postulate that multifactorial impacts of HCV and liver disease on HIV-related nervous system disorders may originate in different anatomical and cellular compartments.

HIV-associated neuropathic pain: epidemiology, pathophysiology and management.

Peripheral neuropathy is associated with numerous systemic illnesses including HIV infection. Neuropathic pain constitutes approximately 25-50% of all pain clinic visits. Distal symmetrical polyneuropathy (DSP) is the most common form of peripheral neuropathy in individuals with HIV infection. DSP is distinguished from other forms of neuropathy on the basis of history and neurological examination. The pain associated with DSP can be debilitating. Therefore, it is important to diagnose HIV-associated DSP properly and treat the neuropathic pain in order to improve quality of life. We review the clinical manifestations, epidemiology, pathophysiology and management strategies for HIV-associated DSP.

HIV-associated distal sensory polyneuropathy in the era of highly active antiretroviral therapy: the Manhattan HIV Brain Bank.

OBJECTIVES: To examine distal sensory polyneuropathy (DSP) in a highly active antiretroviral therapy era, human immunodeficiency virus (HIV)-infected cohort, to determine whether clinical manifestations are affected by demographic or other clinical variables. PATIENTS: One hundred eighty-seven patients with HIV infection enrolled in the Manhattan HIV Brain Bank underwent baseline neurologic evaluations between January 29, 1999, and June 17, 2002. Distal sensory polyneuropathy was diagnosed if patients displayed abnormalities in 2 or more of the following: ankle reflexes or vibratory or pinprick perception. Patients were classified as symptomatic if they described pain, paresthesia, or numbness. Nonneurologic information was obtained by interview, laboratory testing, and medical chart review. Psychiatric and substance use disorders were elucidated by semistructured interview. In 36 patients, morphometric analysis was performed on autopsy-derived sural nerves. RESULTS: Of 187 patients, 99 (53%) had DSP. Patients with neuropathy were older than those without (mean +/- SD age, 45.3 +/- 0.7 vs 41.2 +/- 0.8 years, P <.001), and DSP was significantly more common in men (58% [83/99]) than in women (37% [16/99]) (P =.02). The presence of neuropathy was not correlated with plasma viral load, decreased CD4 cell counts, or neurotoxic antiretroviral therapy. Twenty-six of 99 patients with DSP were asymptomatic. Asymptomatic neuropathy was correlated with histories of opiate and sedative abuse and dependence. Symptomatic DSP correlated with ethanol and hallucinogen syndromes, but not neurotoxic therapy. Sural nerve morphometric findings did not distinguish between patients with substance use syndromes and those without. CONCLUSIONS: In contrast to populations before the era of highly active antiretroviral therapy, DSP in the Manhattan HIV Brain Bank cohort is not associated with increased viral load or decreased CD4 cell counts in this cross-sectional analysis. Symptoms in DSP are associated with substance use disorders, but no difference in morphologic structure is seen in nerves of patients with HIV infection with and without substance use histories. Previously reported virologic and immunologic underpinnings of DSP may be affected by highly active antiretroviral therapy. Furthermore, symptoms of DSP in substance users may be altered by central mechanisms of increased or decreased tolerance to sensory disturbance.

HIV neuromuscular disease and mitochondrial function.

The pathogenesis of neuromuscular syndromes in HIV-infected patients is multifactorial. Of recent concern is the mitochondrial-mediated neuromuscular pathology in HIV and its treatment. We present currently available evidence supporting the role of mitochondrial pathology in the peripheral nerve and muscle disorders due to HIV infection and antiretroviral (ARV) therapy. Three neuromuscular syndromes are discussed: distal symmetric polyneuropathy (DSP), myopathy, and HIV-associated neuromuscular weakness syndrome (HANWS). Myopathy has the most in-vivo data relating to HIV-related mitochondrial pathology, while DSP and HANWS have growing evidence of mitochondrial pathology, particularly in the context of ARV use. It is likely that these neuromuscular disorders result from a combination of mitochondrial and immunological mechanisms due to HIV and ARV therapy.

Neuromuscular complications in HIV.

HIV affects many organs of the body, including the nervous system. As a result, a series of neurologic complications have created challenges for scientists and clinicians alike. Among these, HIV-associated neuropathy and myopathy may occur at all stages of the disease process. Of the neuropathies, distal symmetrical polyneuropathy is the most common form. The pathogenesis of primary HIV neuropathy is unknown. Other types of neuropathy seen in HIV-infected subjects include toxic neuropathy, inflammatory demyelinating polyneuropathy, progressive polyradiculopathy, and mononeuritis multiplex. In this review, we present the clinical manifestations, pathogenesis, diagnosis, and management of different types of neuropathy in HIV infection. Myopathy, another complication of HIV, is not associated with any particular stage of immunosuppression. Symptoms include symmetrical weakness of the proximal muscles in the extremities. Serum creatine kinase levels are often moderately elevated. Electromyography and muscle biopsy are helpful tests for diagnosis. Treatment of HIV myopathy includes corticosteroids, nonsteroidal anti-inflammatory agents, and intravenous immunoglobulin.

Controlling neuropathic pain in HIV.

Neuropathic pain is associated with numerous systemic illnesses, including HIV infection. The diagnosis and management of peripheral neuropathy presents diagnostic and therapeutic challenges. Among various forms of HIV-associated peripheral neuropathies, distal symmetrical polyneuropathy (DSP) is the most common. DSP may be caused or exacerbated by neurotoxic antiretrovirals, particularly the dideoxynucleoside analogues (d-drugs). Selection of appropriate pharmacologic intervention for peripheral neuropathy should be based on efficacy, safety, ease of administration, and cost. We review treatment options for painful HIV neuropathy, including experimental agents studied in recent and ongoing clinical trials.

Controlling Neuropathic Pain in HIV.

Neuropathic pain is associated with numerous systemic illnesses, including HIV infection. The diagnosis and management of peripheral neuropathy presents diagnostic and therapeutic challenges. Among various forms of HIV-associated peripheral neuropathies, distal symmetrical polyneuropathy (DSP) is the most common. DSP may be caused or exacerbated by neurotoxic antiretrovirals, particularly the dideoxynucleoside analogues (d-drugs). Selection of appropriate pharmacologic intervention for peripheral neuropathy should be based on efficacy, safety, ease of administration, and cost. We review treatment options for painful HIV neuropathy, including experimental agents studied in recent and ongoing clinical trials.

A randomized controlled trial of 5% lidocaine gel for HIV-associated distal symmetric polyneuropathy.

OBJECTIVE: To investigate the analgesic efficacy and safety of 5% lidocaine gel in painful HIV-associated distal sensory polyneuropathy (DSP). BACKGROUND: Painful DSP, the most common neurologic complication in HIV infection, is difficult to treat. Lidocaine 5% gel was effective in alleviating neuropathic pain in an open-label study of HIV DSP. METHODS: In a double-blind, placebo-controlled, crossover, multi-center study, 64 subjects were randomized to receive 5% lidocaine or vehicle gel for 2 weeks (phase A). A washout period of 2 weeks was followed by a crossover to the alternate agent for another 2 weeks (phase B). The primary outcome was difference in average pain scores (Gracely pain scale) between the 2 groups during the second week of each treatment period. Secondary outcomes included differential effect of the first treatment, difference in global pain relief, and pain response by neurotoxin exposure. RESULTS: The baseline pain scores of the 2 groups were similar. The average pain scores during the second week of each phase of the lidocaine gel group did not differ from those of the placebo group (phase A: lidocaine 1.09, placebo 1.15; phase B: lidocaine 1.16, placebo 1.10). There also was no difference noted in secondary outcomes. The pain responses of lidocaine gel-treated subjects with current exposure to neurotoxic antiretrovirals (1.18) did not differ compared with those without (1.10) (P = 0.358). There were no significant adverse effects. CONCLUSION: Lidocaine 5% gel is a safe but ineffective agent in the treatment of pain in HIV-associated DSP.