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BACKGROUND: Sensory neuropathy (SN) is a common and often painful neurological condition associated with HIV-infection and its treatment. However, data on the incidence of SN in neuropathy-free individuals initiating combination antiretroviral therapies (cART) that do not contain the neurotoxic agent stavudine are lacking. AIMS: We investigated the six-month incidence of SN in ART naive individuals initiating tenofovir (TDF)-based cART, and the clinical factors associated with the development of SN. METHODS: 120 neuropathy-free and ART naive individuals initiating cART at a single centre in Johannesburg, South Africa were enrolled. Participants were screened for SN using clinical signs and symptoms at study enrolment and approximately every two-months for a period of approximately six-months. Diagnostic criteria for symptomatic SN was defined by the presence of at least one symptom (pain/burning, numbness, paraesthesias) and at least two clinical signs (reduced vibration sense, absent ankle reflexes or pin-prick hypoaesthesia). Diagnostic criteria for asymptomatic SN required at least two clinical signs only (as above). RESULTS: A total of 88% of the cohort completed three visits within the six-month period. The six-month cumulative incidence of neuropathy was 140 cases per 1000 patients (95% CI: 80 - 210) at an incidence rate of 0.37 (95% CI: 0.2 - 0.5) per person year. Height and active tuberculosis (TB) disease were independently associated with the risk of developing SN (p < 0.05). INTERPRETATION: We found that within the first six months of starting cART, incident SN persists in the post-stavudine era, with eleven (9%) of individuals developing asymptomatic SN, and nine (8%) developing symptomatic SN. This article is protected by copyright. All rights reserved.