Can we predict neuropathy risk before stavudine prescription in a resource-limited setting?

A toxic sensory neuropathy associated with exposure to inexpensive nucleoside analogue reverse transcriptase inhibitors (NRTIs) [particularly stavudine (d4T)] causes dilemmas in the management of patients with HIV, especially in resource-poor settings. Here patients (n = 96) attending Pokdisus AIDS Clinic at the Cipto Mangunkusumo Hospital, Jakarta who had been treated with d4T were screened for symptomatic neuropathy. Clinical, demographic, and genetic factors were considered as possible neuropathy risk factors. DNA from saliva was used to examine alleles of TNFA-308, BAT1 (intron 10), TNFA-1031, IL1A+4845, and IL12B (3' UTR). The prevalence of neuropathy (symptoms and signs) was 34%. On multivariate analysis, neuropathy following d4T exposure was associated with increasing age, increasing height, and TNFA-1031*2 (model p = 0.0009). Isoniazid exposure (present in 56% of patients) was not associated with neuropathy in this cohort, where all patients had received pyridoxine coadministration. These data suggest that a simple algorithm based on patient age, height, and TNF genotype could be used to predict the individual's risk of symptomatic neuropathy prior to prescription of d4T.