title: Isoniazid exposure and pyridoxine levels in human immunodeficiency virus associated distal sensory neuropathy.
abstract: METHODS
  Distal sensory polyneuropathy (DSP) may manifest in human immunodeficiency virus (HIV) infected individuals before or after antiretroviral therapy (ART). DSP can also occur in response to isoniazid (INH); this can be prevented by pyridoxine supplementation. N-acetyltransferase 2 (NAT2) polymorphisms influence drug acetylation and possibly the risk for INH-associated DSP.
  
  
  OBJECTIVE
  To investigate the relationship between previous/current TB, pyridoxine deficiency and DSP in HIV-infected individuals enrolled in a government-sponsored HIV programme.
  
  
  METHODS
  Neuropathy assessments were performed among 159 adults pre-ART and 12 and 24 weeks thereafter. DSP was defined as ⩾1 neuropathic symptom and sign. NAT2 genotypes predicted acetylation phenotype. Serum pyridoxine levels (PLP) were quantified at baseline and week 12.
  
  
  RESULTS
  DSP was present in 16% of individuals pre-ART and was associated with previous/current TB (P = 0.020). Over 50% were pyridoxine deficient (PLP < 25 nmol/l), despite supplementation with vitamin B complex supplements (2-4 mg/day pyridoxine). Those with a history of TB and pre-ART DSP were more likely to be pyridoxine deficient (P = 0.029), and slow/intermediate NAT2 phenotypes impacted on their PLP levels. Incident/worsening DSP after ART developed in 21% of the participants. PLP levels remained low after ART, particularly among those with prior TB, but without an association between DSP or NAT2 phenotypes.
  
  
  CONCLUSIONS
  Adequate pyridoxine supplementation before ART initiation should be prioritised, particularly in those with a history of TB or current TB.
authors.affiliation: Division of Neurology, Department of Medicine, University of Cape Town, Observatory, South Africa.
authors.forename: J J
authors.initials: JJ
authors.lastname: van der Watt
authors.affiliation: Departments of Neurology and Public Health Sciences, University of Miami, Miami, Florida, USA.
authors.forename: M G
authors.initials: MG
authors.lastname: Benatar
authors.affiliation: Department of Neurology, Emory University, Atlanta, Georgia, USA.
authors.forename: T B
authors.initials: TB
authors.lastname: Harrison
authors.affiliation: School of Public Health and Family Medicine, University of Cape Town, Observatory, South Africa.
authors.forename: H
authors.initials: H
authors.lastname: Carrara
authors.affiliation: Division of Neurology, Department of Medicine, University of Cape Town, Observatory, South Africa.
authors.forename: J M
authors.initials: JM
authors.lastname: Heckmann
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D001191:Arylamine N-Acetyltransferase / Q000235:genetics; D060085:Coinfection / Q000188:drug therapy; D005260:Female; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D007538:Isoniazid / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D011115:Polyneuropathies / Q000175:diagnosis* / Q000188:drug therapy*; D011736:Pyridoxine / Q000097:blood*; D012307:Risk Factors; D013019:South Africa; D014376:Tuberculosis / Q000188:drug therapy; D026681:Vitamin B 6 Deficiency / Q000175:diagnosis*; D014803:Vitamin B Complex / Q000627:therapeutic use*
chemical_list: D014803:Vitamin B Complex; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human; D011736:Pyridoxine; D007538:Isoniazid