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Higher iron stores and the HFE 187C>G variant delay onset of peripheral neuropathy during combination antiretroviral therapy.
Kallianpur, Asha R; Wen, Wanqing; Erwin, Angelika L; Clifford, David B; Hulgan, Todd; Robbins, Gregory K.
Afiliação
  • Kallianpur AR; Genomic Medicine Institute, Cleveland Clinic/Lerner Research Institute, Cleveland, Ohio, United States of America.
  • Wen W; Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, United States of America.
  • Erwin AL; Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States of America.
  • Clifford DB; Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
  • Hulgan T; Genomic Medicine Institute, Cleveland Clinic/Lerner Research Institute, Cleveland, Ohio, United States of America.
  • Robbins GK; Division of Infectious Diseases, Departments of Medicine and Neurology, Washington University School of Medicine, Saint Louis, Missouri, United States of America.
PLoS One ; 15(10): e0239758, 2020.
Article em En | MEDLINE | ID: mdl-33057367
ABSTRACT

OBJECTIVE:

People with HIV (PWH) continue to experience sensory neuropathy and neuropathic pain in the combination antiretroviral therapy (cART) era for unclear reasons. This study evaluated the role of iron in a previously reported association of iron-loading hemochromatosis (HFE) gene variants with reduced risk of neuropathy in PWH who received more neurotoxic cART, since an iron-related mechanism also might be relevant to neuropathic symptoms in PWH living in low-resource settings today.

DESIGN:

This time-to-event analysis addressed the impact of systemic iron levels on the rapidity of neuropathy onset in PWH who initiated cART.

METHODS:

Soluble transferrin receptor (sTFR), the sTFR-ferritin index of iron stores, and high-sensitivity C-reactive protein (hsCRP) levels were determined in stored baseline sera from participants of known HFE genotype from AIDS Clinical Trials Group (ACTG) Study 384, a multicenter randomized clinical trial that evaluated cART strategies. Associations with incident neuropathy were evaluated in proportional-hazards, time-to-event regression models, adjusting for potential confounders.

RESULTS:

Of 151 eligible participants with stored serum who were included in the original genetic study, 43 had cART-associated neuropathy; 108 had sufficient serum for analysis, including 30 neuropathy cases. Carriers of HFE variants had higher systemic iron (lower sTFR and sTFR-ferritin index) and lower hsCRP levels than non-carriers (all p<0.05). Higher sTFR or iron stores, the HFE 187C>G variant, and lower baseline hsCRP were associated with significantly delayed neuropathy in self-reported whites (n = 28; all p-values<0.05), independent of age, CD4+ T-cell count, plasma HIV RNA, and cART regimen.

CONCLUSIONS:

Higher iron stores, the HFE 187C>G variant, and lower hsCRP predicted delayed onset of neuropathy among self-reported white individuals initating cART. These findings require confirmation but may have implications for cART in HIV+ populations in areas with high endemic iron deficiency, especially those PWH in whom older, more neurotoxic antiretroviral drugs are occasionally still used.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Variação Genética / Doenças do Sistema Nervoso Periférico / Terapia Antirretroviral de Alta Atividade / Antirretrovirais / Proteína da Hemocromatose / Ferro Tipo de estudo: Clinical_trials / Prognostic_studies Limite: Adult / Female / Humans / Male Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Variação Genética / Doenças do Sistema Nervoso Periférico / Terapia Antirretroviral de Alta Atividade / Antirretrovirais / Proteína da Hemocromatose / Ferro Tipo de estudo: Clinical_trials / Prognostic_studies Limite: Adult / Female / Humans / Male Idioma: En Ano de publicação: 2020 Tipo de documento: Article