DOI: 10.1097/QAI.0b013e3180ed44d9
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PMID: 17895769
Issn Print: 1525-4135
Publication Date: 2007/10/01
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Excerpt
Peripheral neuropathy (PN) is a frequent complication of HIV infection, but its actual mechanisms are largely unknown.1 Kallianpur et al2 showed that patients with HFE (hemochromatosis) gene mutations, the C282Y heterozygosis mutation in particular, had a decreased risk of PN. It has been hypothesized that peripheral nervous system damage is facilitated by decreased iron storage related to HIV infection and that HFE mutations compensate for this phenomenon. Although this observation has potential implications for patient risk assessment and treatment, it has been obtained in a limited population under specific highly active antiretroviral therapy (HAART), including stavudine (d4T) and didanosine (ddI). Moreover, diagnosis of PN was based on patient self-reporting of symptoms without any confirmation by electromyography. In this study, we aimed at assessing the possible protective effect of HFE mutations, taking into account potential codeterminants of PN, whose diagnosis was confirmed by electromyography.
A case-control study was performed. All patients with a diagnosis of PN confirmed by electromyography (ie, cases) among HIV-positive patients attending the Clinic of Infectious and Tropical Diseases of the University of Brescia were studied. Patients who did not have signs or symptoms of PN (ie, controls) were selected from the same clinic and matched with cases for the following factors: age (±5 years), gender, reported history of alcohol abuse (defined as alcohol consumption exceeding 60 g of ethanol per day), hepatitis C virus (HCV) antibody (Ab) reactivity, hepatitis B surface antigen (HBsAg)-positive serostatus, and concomitant diabetes. The possible influence of other factors that may also cause PN was explored: risk factors for HIV acquisition; nadir CD4+ T-cell count; occurrence of previous major opportunistic infections (eg, 1993 Centers for Disease Control and Prevention [CDC] clinical class C); exposure to dideoxynucleoside analogues (ddX), such as d4T, ddI, and zalcitabine; and HIV RNA level. To reduce confounding, we excluded patients with other strong risk factors for PN (eg, exposure to drugs toxic for the nerves, cancer, autoimmune diseases).
Analyses of exons 2 and 4 of the HFE gene, mainly aimed at detecting the H63D and C282Y mutations, were performed by denaturing high-performance liquid chromatography (HPLC) as previously described.3
The data were analyzed by a conditional logistic regression model to account for matched case-control data and to identify variables associated with outcome (ie, PN). Variables reaching P ≤ 0.2 on univariate analysis were put into the multivariable model, including HFE gene mutations. Results are expressed as odds ratios (ORs) with their 95% confidence intervals (CIs). Analyses were performed with STATA (STATA Statistical Software, release 9.0; Stata Corporation, College Station, TX).
We studied 57 HIV-positive patients with from PN and 57 HIV-positive controls. Patient characteristics used for matching were as follows: 95% Italian nationality, 82% male gender, mean age of 45 (SD = 5) years, 61% HCV-Ab-positive serostatus, 19% alcohol abusers, and 5% diabetics. Most patients (35 [61%] of 57) in the case group had 3 or more possible risk factors for PN (among alcohol abuse, diabetes, HCV-Ab reactivity, CD4 nadir <100 cells/mm3, CDC clinical class C, HIV RNA >5 log10 copies/mL at the time of electromyography, and ddX exposure). The prevalence of HFE gene mutations did not seem significantly different between the cases and the controls. Sixty-three percent of patients in the case group had no HFE mutations, 25% had H63D heterozygosis, 5% had H63D homozygosis, and 7% had C282Y heterozygosis. Among the controls, 73% had no HFE mutations, 25% had H63D heterozygosis, and 2% had H63D homozygosis.
Table 1 shows results of the conditional logistic regression analysis.
