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Oral Abstracts and Mini-Lecture|
Neuropathogenic Manifestations of HIV Infection
Monday, 10 - 12:30 pm
Presentation Time: 12 pm
Background More than one third of patients with HIV/AIDS have peripheral neuropathy. However, peripheral neuropathy is frequently misdiagnosed, particularly by non-neurological clinicians. Recent cohort studies have provided data on the reliability of brief screening batteries in the diagnosis of neuropathy, in comparison to comprehensive neurological and quantitative assessments. The type, frequency, and mechanisms of peripheral neuropathies in HIV infection vary with the stage of HIV disease. Several risk factors predispose patients to the development of peripheral neuropathy, including advancing age and immunosuppression. There is an association between increased plasma HIV virus load and clinical measures of neuropathy, particularly pain, quantitative sensory tests, and epidermal nerve fiber densities. Numerous other disorders associated with neuropathy are common in HIV-infected patients, particularly alcohol abuse, entrapment neuropathies, diabetes mellitus, and hepatitis C. The use of specific dideoxynucleoside analogue ARV (d-drugs)―specifically didanosine (ddI), zalcitabine (ddC), and stavudine (d4T) ―may be limited by peripheral nervous system toxicity. While some d-drugs are unequivocally neurotoxic, it is possible that their adverse effects on the peripheral nerve are counterbalanced by their salutary affects on virological control. Reduction in plasma HIV RNA results in improvement in quantitative sensory thermal thresholds, and future studies will assess whether these effects translate to clinical improvement in neuropathic symptoms. There is mounting evidence that nucleoside-related toxic neuropathy is caused by mitochondrial toxicity. The recently described HIV-associated neuromuscular weakness syndrome, associated in many patients with elevated serum lactate level and nucleoside analogue therapy, adds further support to this mechanism. Numerous palliative agents have been studied for their effect on pain reduction in HIV neuropathy. Negative results emerged from placebo-controlled studies of acupuncture, topical lidocaine gel, amitryptiline, mexiletine, and peptide T. The anticonvulsant, lamotrigine, resulted in significant pain relief, although results were superior to placebo only in patients on d-drug ARV regimens. Following promising results of an open-label study, a large placebo-controlled trial is examining the safety and efficacy of the high concentration capsaicin patch. Conclusions: Pathogenesis-based therapies may provide both analgesic and restorative effects in peripheral neuropathy. Recombinant human nerve growth factor produced pain relief in HIV neuropathy, but did not show regenerative effects. Within the ACTG, a novel agent, Prospatide, is under study for HIV neuropathy (A5180). Other agents in this class with trials in development include L-acetyl carnitine, and the class of neurophilin ligands derived from cyclosporine and FK506.
Keywords: HIV-1 restriction; TRIM5alpha; Old World Monkeys