title: Sensory polyneuropathy in human immunodeficiency virus-infected patients receiving tuberculosis treatment.
abstract: METHODS
  Human immunodeficiency virus (HIV) infection and treatments for HIV infection and tuberculosis (TB) are associated with the risk of developing sensory polyneuropathy (SPN). Vitamin B6 and genetically determined slow isoniazid (INH) acetylation are believed to play key roles in the development of SPN in a TB treatment setting.
  
  
  OBJECTIVE
  To investigate slow acetylation and risk factors for SPN in HIV-infected patients receiving TB treatment, and establish vitamin B6 status and its association with SPN.
  
  
  METHODS
  HIV-infected in-patients were prospectively assessed after initiating TB treatment and vitamin B6 supplementation, and monthly during hospitalisation. SPN was defined as ≥1 symptom plus ≥1 sign. NAT2 genotyping predicted acetylation status, and plasma high performance liquid chromatography estimated vitamin B6 status. A survival analysis estimated hazard ratios (HRs) for SPN during TB treatment.
  
  
  RESULTS
  Of 116 participants, 56% had SPN at study entry. Participants developed SPN at a rate of 26/100 person-months (95%CI 18-35) during TB treatment, which was independently associated with slow acetylation (HR 2.5; 95%CI 1.1-5.9), as well as black race, previous TB and extra-pulmonary/disseminated TB. Vitamin B6 status was normal, irrespective of SPN.
  
  
  CONCLUSIONS
  Risk factors for SPN suggest a multi-factorial pathogenesis related to INH and other potential nervous system insults. SPN developed despite normal vitamin B6 status, suggesting other mechanisms of injury.
authors.affiliation: Neurology Research Group, Department of Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: C M
authors.initials: CM
authors.lastname: Centner
authors.affiliation: School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: H
authors.initials: H
authors.lastname: Carrara
authors.affiliation: Department of Neurology, Emory University, Atlanta, Georgia, USA.
authors.forename: T B
authors.initials: TB
authors.lastname: Harrison
authors.affiliation: Department of Neurology, University of Miami, Miami, Florida, USA.
authors.forename: M
authors.initials: M
authors.lastname: Benatar
authors.affiliation: Neurology Research Group, Department of Medicine, University of Cape Town, Cape Town, South Africa; Division of Neurology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: J M
authors.initials: JM
authors.lastname: Heckmann
mesh_terms: D000107:Acetylation; D000328:Adult; D000995:Antitubercular Agents / Q000009:adverse effects*; D001191:Arylamine N-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D019587:Dietary Supplements; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000150:complications* / Q000175:diagnosis / Q000401:mortality; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D010641:Phenotype; D011115:Polyneuropathies / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology; D011446:Prospective Studies; D012307:Risk Factors; D011984:Sensory Receptor Cells; D013997:Time Factors; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D025101:Vitamin B 6 / Q000097:blood / Q000627:therapeutic use; D026681:Vitamin B 6 Deficiency / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy; D014815:Vitamins / Q000627:therapeutic use
chemical_list: D000995:Antitubercular Agents; D014815:Vitamins; D025101:Vitamin B 6; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human