title: Effects of a reduced dose of stavudine on the incidence and severity of peripheral neuropathy in HIV-infected adults in South Africa.
abstract: BACKGROUND
  Although recent World Health Organization (WHO) guidelines recommend withdrawing stavudine (d4T) from first-line antiretroviral therapy (ART), it remains commonly used in resource-limited settings. In 2006, WHO recommended decreasing the dose of d4T from 40 mg to 30 mg to mitigate toxicities. We compared the incidence and severity of peripheral neuropathy by d4T dose in a retrospective cohort study.
  
  
  METHODS
  Patients' charts from an ART-naive population at a rural clinic in KwaZulu-Natal, South Africa, were retrospectively reviewed for signs and symptoms of incident peripheral neuropathy and were graded for severity using the DAIDS scale. Patients enrolled prior to the WHO guideline change were included in the study if they were on d4T 40 mg for ≥6 months. After the guideline change all patients were initiated on d4T 30 mg.
  
  
  RESULTS
  A total of 475 patients were analysed, including 235 in the 40 mg cohort (152.7 person-years [py]) and 240 in the 30 mg cohort (244.7 py). Incidence of peripheral neuropathy was 90.4/100 py (95% CI 75.9, 106.8) in the 40 mg cohort versus 40.5/100 py (95% CI 32.9, 49.3) in the 30 mg group (incidence rate ratio 0.45; P<0.0001). There was no difference in proportion of severe peripheral neuropathy cases (grade 3/4) between the cohorts: 8.3% in the 40 mg group and 8.9% in the 30 mg group (P=1.0). In a multivariate analysis, risk of peripheral neuropathy was associated with increasing age (hazard ratio [HR] 1.65, 95% CI 1.24, 2.19), 40 mg dose (HR 2.1, 95% CI 1.61, 2.74) and concurrent tuberculosis therapy (HR 1.41, 95% CI 1.06, 1.87).
  
  
  CONCLUSIONS
  Incidence of peripheral neuropathy in the 40 mg cohort was extremely high and, although lower, the rate in the 30 mg cohort was nonetheless unacceptably high.
authors.affiliation: Division of Infectious Diseases, Weill Cornell Medical College, New York, NY, USA. mep2002@med.cornell.edu
authors.forename: Meera
authors.initials: M
authors.lastname: Pahuja
authors.forename: Anneke
authors.initials: A
authors.lastname: Grobler
authors.forename: Marshall J
authors.initials: MJ
authors.lastname: Glesby
authors.forename: Farina
authors.initials: F
authors.lastname: Karim
authors.forename: Gary
authors.initials: G
authors.lastname: Parker
authors.forename: Sizwe
authors.initials: S
authors.lastname: Gumede
authors.forename: Kogieleum
authors.initials: K
authors.lastname: Naidoo
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D015658:HIV Infections; D006801:Humans; D015994:Incidence; D008297:Male; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced*; D017410:Practice Guidelines as Topic; D012189:Retrospective Studies; D013019:South Africa; D018119:Stavudine / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D018119:Stavudine