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.

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.

Effects of dietary fiber in vervet monkeys fed "Western" diets.

Male Vervet monkeys (7/treatment) were fed a "Western" diet containing 46.2% calories as fat, 39.8% as carbohydrate and 14.0% as protein. The diet was augmented with 10% cellulose or 10% pectin. A third (control) group of seven monkeys was fed a commercial ration augmented with fruit and bread. After 34 weeks, serum cholesterol levels were elevated significantly in the two test groups compared with the controls but there was no difference between the two fiber-fed groups. Serum triglycerides were unaffected. Liver cholesterol levels were the same in all three groups but liver triglyceride levels were lower in the monkeys fed cellulose. Biliary lipids were similar in all three groups as were the calculated lithogenic indices. The average aortic sudanophilia (percent of total area) in the three groups was cellulose, 10.6 +/- 2.5; pectin, 8.1 +/- 2.5; and control, 1.1 +/- 0.4. One animal in each of the groups fed "Western" diet exhibited an atherosclerotic plaque. The results indicate that there is no difference between pectin and cellulose with regard to their effects on either lipidemia or aortic sudanophilia in Vervet monkeys fed a Western-type diet.