This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. While antiretroviral therapy has greatly reduced the annual number of AIDS diagnoses and deaths, peripheral neuropathy is the most frequent neurological complication associated with HIV-1 and AIDS. The majority of these fall into one of two forms of distal sensory polyneuropathy: distal symmetrical polyneuropathy (DSPN) and antiretroviral drug toxic neuropathy (ATN.) Symptoms are usually characterized by dysesthesias (burning and painful soles), paresthesias, and/or numbness in the extremities. Many of the therapies used in treating HIV have resulted in an antiretroviral drug toxic neuropathy as an adverse effect, most frequently, dideoxynucleoside class of drugs. Peripheral neurotoxicity is dose-dependent and may be a limiting factor in antiretroviral therapy, and one-third of antiretroviral drug toxic neuropathy cases may fail to improve upon discontinuing the drug. Topical capsaicin treatment represents a strategy to selectively reduce the hyperactivity of peripheral nociceptive nerves, which may consequently relieve neuropathic pain. The purpose of the study is to assess the efficacy, safety and tolerability of NGX-4010 [CAPREVE Patch (capsaicin 640 g/cm2)] a topical, dermal capsaicin patch at three different dose levels (i.e., application durations) for the treatment of painful HIV-associated neuropathy resulting from HIV disease and/or antiretroviral drug exposure. Based on these data, an optimal dose for treatment of painful HIV-associated neuropathy will be selected. The study will also provide information about the efficacy, safety and tolerability of repeated treatments with the CAPREVE patch over one year. Early studies in lamotrigine and gabapentin for the treatment of painful neuropathy have proven effective, but both of these drugs are centrally active and possess significant side effect risk to patients. Systemic treatments of HIV/AIDS patients must always take into account drug interactions with the disease and oftentimes many other concomitant medications. A single treatment with a dermal high-concentration capsaicin patch that will be applied with topical anesthesia may reduce the frequency and severity of neuropathic pain for several months. In addition, there appears to be little or no systemic absorption of capsaicin following use of the CAPREVE patch, the potential for drug-drug or drug-virus interactions is very low.
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