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

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 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. DESIGN: 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. CONCLUSION: Adequate pyridoxine supplementation before ART initiation should be prioritised, particularly in those with a history of TB or current TB.

Sensory polyneuropathy in human immunodeficiency virus-infected patients receiving tuberculosis treatment.

SETTING: 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.

Polyneuropathy, anti-tuberculosis treatment and the role of pyridoxine in the HIV/AIDS era: a systematic review.

Tuberculosis (TB) is increasing in incidence in certain parts of the world, particularly where there is a co-epidemic of human immunodeficiency virus/acquired immune-deficiency syndrome (HIV/AIDS), and it is associated with a significant degree of morbidity and mortality. One of the most common complications of anti-tuberculosis treatment is the development of a painful isoniazid (INH) associated polyneuropathy (PN), which is preventable with adequate pyridoxine supplementation. As PN is also the most frequent neurological complication associated with HIV infection, subjects who are HIV and TB co-infected may be at increased risk of developing PN. In this review, we explore current knowledge of anti-tuberculosis drug associated PN focusing on INH and its relationship to pyridoxine, as well as the additional impact of antiretroviral treatment and TB-HIV co-infection. It is evident that guidelines established for the prevention and treatment of this problem differ between industrialised and developing countries, and that further research is needed to define the optimum dosing of pyridoxine supplementation in populations where there is a significant burden of TB and HIV.