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Peripheral neuropathies often affect patients with HIV disease,1 and various peripheral neuropathies have been described at different stages of HIV infection, from seroconversion to AIDS. Acute inflammatory demyelinating polyneuropathies have been found in association with primary HIV infection; chronic inflammatory demyelinating polyneuropathies, isolated mononeuritis, and multiplex mononeuritis have more commonly been described in those in advanced stages of HIV disease, and distal symmetric polyneuropathy has been found to be the most common neuropathy among persons with AIDS. In most cases, the aetiopathogenesis of these neuropathies is still unclear, although various factors have been implicated (infectious, metabolic, immunological, inflammatory, nutritional, and toxic).2 To date, relatively few studies have estimated the incidence of peripheral neuropathies among HIV infected patients belonging to different population groups. Data derived from the Multicenter AIDS Cohort Study showed annual rates slightly higher than 1.5/100 person-years for sensory neuropathy.3 Another study found a roughly 1% annual incidence of neuropathies in symptomatic patients without AIDS.4 To estimate the incidence of peripheral neuropathies during the different stages of HIV disease, we analysed data from a cohort study of patients with known dates of seroconversion (a documented HIV seronegative test followed by a confirmed positive test within two years). The seroconversion date was estimated as the midpoint in time between the last negative and the first positive HIV test. After seroconversion, patients were followed up to obtain clinical information and data on laboratory indices about every six months. The study design and methodology have been described in detail elsewhere.5 The present analysis included four clinical centres, which performed a detailed neurological examination of the participants of the study. These centres were contacted to provide complete information on peripheral neuropathies by completing a standardised data collection form for each episode, providing detailed information on diagnostic criteria (neurological signs and symptoms, instrumental diagnosis), AIDS prophylaxis, and antiretroviral drug therapy. The study population consisted of 621 HIV seroconverters. The median age of the participants was 27 (range 14–66) years, 29 for males and 24 for females. Of these patients; 267 (42.9%) were intravenous drug users, 217 (34.9%) were homosexual men, and 127 (20.5%) were heterosexual contacts; 10 (1.6%) patients had unknown or undetermined risk factors.During a median follow up time of 5.7 years, 19 (3.1%) patients developed symptoms suggestive of peripheral neuropathies. The estimated incidence of peripheral neuropathies was 5.5/1000 person-years of follow up. The median age at the time of diagnosis was 35.2 years (range 24.8–53.6 years). Thirteen events (68.4%) occurred among males and six (31.6%) among females. For the exposure category, peripheral neuropathy was found among seven (2.6%) intravenous drug users, five (2.3%) homosexual men, and seven (5.51%) heterosexual contacts. The incidence rate of peripheral neuropathies was 4.4/1000 person-years in intravenous drug users, 4.3/1000 person-years in homosexual men, and 11.4/1000 person-years in heterosexual contacts. Acute infection was observed in 43 of 621 (7%) patients. One episode of peripheral neuropathy occurred during acute infection (the incidence rate of peripheral neuropathies was 42.4/100 person-years), six episodes during the asymptomatic phase (0.2/100 person-years), eight in the pre-AIDS symptomatic phase (2.4/100 person-years), and four episodes in patients who had already presented with diseases indicative of AIDS (3.8/100 person-years). The CD4 cell count at diagnosis of peripheral neuropathies was 266.2 for the patients with acute infection; the median was 324.6 (range 149.7–655.2) for those in the asymptomatic phase, 216.5 (range 14.9–1440.0) among those with pre-AIDS symptoms, and 38.0 (range 7.2–124.8) among persons with AIDS. Of the 19 patients with peripheral neuropathies, 15 (78.9%) had distal symmetric polyneuropathy, two (10.5%) had multiplex mononeuritis, and two (10.5%) acute inflammatory demyelinating polyneuropathies. The median CD4 cell count at diagnosis of peripheral neuropathy was 31.2 (range 16.3–47.0) for persons with multiplex mononeuritis, 184.1 (range 7.5–655.4) for those with distal symmetric polyneuropathy, and 304.3 (range 342.1–266.3) for those with multiplex mononeuritis All 19 patients had sensory neuropathy, and 14 (73.7%) also had motor impairment. Of these 19 patients, 13 (68.4%) underwent electrophysiological investigations, showing abnormalities of nerve conduction. Another patient presenting with a mononucleosis-like syndrome and meningoradiculoneuritis had a raised number of cells (184/μl) in the CSF. The CSF of the other participants was normal. No participant reported the use of known neurotoxic drugs such as DDC; 10 patients had received AZT and two had received DDI (both patients who were treated with DDI had discontinued treatment six months before the onset of peripheral neuropathies; one had multiplex mononeuritis and one distal symmetric polyneuropathy). Only one participant reported alcohol misuse. In conclusion, the incidence of peripheral neuropathies seems to be high among patients with acute HIV disease, although in our study the number of patients with acute disease was not very high. In the asymptomatic phase, the incidence of peripheral neuropathies was low, with a tendency to increase in the advanced stages of HIV infection. Our findings are in accord with the results of other studies4 which showed that the development and progression of neuropathy was correlated with the progression of HIV disease. The issue of peripheral nerve disorders in HIV infection should not be neglected, as the symptoms of peripheral neuropathy may be extremely painful and debilitating and may complicate the management of HIV positive patients, negatively influencing the quality of their life.
This work was supported by the Ministero della Sanità-Istituto Superiore di Sanità, Project grant 940R, 1996.