Isoniazid exposure and pyridoxine levels in human immunodeficiency virus associated distal sensory neuropathy

J. J. Van Der Watt, M. G. Benatar, T. B. Harrison, H. Carrara, J. M. Heckmann

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


SETTING: 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 INHassociated DSP. OBJECTIVE : To investigate the relationship between previous/current TB, pyridoxine deficiency and DSP in HIV-infected individuals enrolled in a governmentsponsored HIV programme. D E S I G N : 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. RESULT S : DSP was present in 16% of individuals pre- ARTand 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. CONCLUS ION: Adequate pyridoxine supplementation before ART initiation should be prioritised, particularly in those with a history of TB or current TB.

Original languageEnglish (US)
Pages (from-to)1312-1319
Number of pages8
JournalInternational Journal of Tuberculosis and Lung Disease
Issue number11
StatePublished - Nov 1 2015


  • Acetylation
  • NAT2
  • Nutrition
  • Tuberculosis
  • Vitamin B6

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Infectious Diseases


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