8th Annual Retrovirus Conference
Adverse events--neuropathy & lipodystrophy in primary infection: Summary of presentations on lipodystrophy and adverse events
Dr. Gilbert Kaufmann, Med. Poliklinik, University Hospital Basel, Petersgraben, Switzerland
Session 31, State of the art lecture HIV related peripheral neuropathy Justin McArthur, Johns Hopkins Univ. School of Medicine, Baltimore
In an elegant presentation McArthur gave an update on the current knowledge and understanding of the pathogenesis of HIV-1 related peripheral neuropathy. Peripheral neuropathy affects 30% of HIV-1 infected subjects and significantly reduces the quality of life. It occurs as an HIV-1 associated complication or as the result of nucleoside analogue toxicity or as a result of HIV immune dysfunction. It manifests as a sensory neuropathy. Patients suffer from burning sensations and paresthesias.
In the Multicenter AIDS Cohort Study (MACS) an association has been found between the viral set point (viral load after the acute phase of HIV-1 infection) and the incidence of peripheral neuropathy. Over 10 years 25% of individuals with high a viral set point develop peripheral neuropathy. Several risk factors for the development of peripheral neuropathy have been identified including higher age, wasting, ApoE4 levels, low CD4 counts and pre-existing neuropathies. In histological examinations, a loss of sensory fibers can be found. Sensory fibers are swollen and an inflammatory infiltrate of macrophages at the peripheral sites can be found. Inflammatory signs can also be observed in dorsal ganglia (cells in the brain). Proinflammatory cytokines such as TNF-alpha are upregulated. The pathogenesis of peripheral neuropathy is unclear. McArthur presented a hypothesis which assumes a macrophage mediated inflammation of nerve fibers result in alterations of sodium channels and sprouting of Ab fibers.
Another possible mechanism is mitochondrial toxicity. ddX nucleosides (ddI, ddC) may inhibit mitochondrial DNA polymerase g and thereby cause a damage to the mitochondria. Support for this hypothesis comes from another abstract (session 4, abstract 9) presented by Brew et al. who found a significant relationship between elevated serum lactate levels and the occurrence of nucleoside analogue associated peripheral neuropathy. Moreover, a positive relationship has been found between the concentration of mitochondrial DNA and the density of nerve fibers. The incidence of peripheral neuropathy is highest for ddC, followed by ddI and d4T. Treatment is difficult and consists primarily in a discontinuation of the causative agent. In controlled studies no significant effect of amitriptyline, accupuncture and local injections of lidocaine has been found. However, lamotrigine (an antiepileptic agent) and recombinant human nerve growth factor (rhNGF) could improve symptoms associated wit peripheral neuropathy.
At the end of his presentation McArthur pointed out that peripheral neuropathy is a heterogeneous entity. More research needs to be done with regard to the pathogenesis and therapy of peripheral neuropathy.
Abstract 403: Early Occurrence of Lipodystrophy in HIV-I-Infected Patients Treated during Primary Infection.
Goujard et al. presented on behalf of the Primo group a study which described the incidence of clinical lipodystrophy (LD) in a prospective cohort of 121 patients diagnosed during primary HIV-I infection who were treated for more than 6 months. Twenty-two patients (18.2%) presented with at least one LD abnormality after a mean follow-up of 24 months. The cumulative incidence of LD was 6% at 12, 18% at 24 and 30% at 36 months.
This study confirms previous reports that lipodystrophy similarly occurs in patients treated early during primary HIV-1 infection.