Peripheral neuropathy (PN) is common in the setting of antiretroviral (ARV) programmes in resource-limited settings and poses significant challenges in assessment and management. A retrospective analysis was undertaken of prevalence and management of PN in a cohort of 3341 patients on highly active antiretroviral therapy. A first line ARV regimen containing stavudine (D4T) is used for clinically eligible patients. Amitriptyline is prescribed for symptom relief and in cases of persistent or escalating symptoms zidovudine (AZT) is substituted for D4T. Leg pain or numbness was reported in 1173 patients (35%). However, only 428 (13%) were given a diagnosis of PN, 228 (7%) were prescribed amitriptyline and 200 (6%) were switched to AZT. A recent pharmokinetic study in this population showed a high Cmax of D4T with the generic combination triomune (D4T 40 mg). This could account for the high prevalence of PN. The optimum time for switch to a non-D4T containing regimen is unknown.