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

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

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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
Volume19
Issue number11
DOIs
StatePublished - Nov 1 2015

Fingerprint

Pyridoxine
Polyneuropathies
Isoniazid
HIV
Acetyltransferases
Acetylation
Phenotype
Therapeutics
Vitamin B 6 Deficiency
Vitamin B Complex
Signs and Symptoms
Genotype

Keywords

  • Acetylation
  • NAT2
  • Nutrition
  • Tuberculosis
  • Vitamin B6

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Infectious Diseases

Cite this

Isoniazid exposure and pyridoxine levels in human immunodeficiency virus associated distal sensory neuropathy. / Van Der Watt, J. J.; Benatar, Michael G; Harrison, T. B.; Carrara, H.; Heckmann, J. M.

In: International Journal of Tuberculosis and Lung Disease, Vol. 19, No. 11, 01.11.2015, p. 1312-1319.

Research output: Contribution to journalArticle

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abstract = "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.",
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