title: Prevalence, incidence and predictors of peripheral neuropathy in African adults with HIV infection within the DART trial.
abstract: OBJECTIVE
  We investigated the prevalence, incidence and predictors of new peripheral neuropathy episodes in previously untreated, symptomatic HIV-infected Ugandan/Zimbabwean adults initiating zidovudine-based antiretroviral therapy (ART).
  
  
  METHODS
  An open-label, multicentre, randomized trial.
  
  
  METHODS
  Peripheral neuropathy was self-reported at 12-weekly clinic visits. Cox regression models (excluding participants reporting preexisting peripheral neuropathy at ART initiation), considered sex; pre-ART WHO stage, age and CD4(+) cell count; CD4(+) cell count versus no CD4(+) cell count monitoring; and time-updated CD4(+) cell count, weight and use of stavudine, isoniazid and didanosine.
  
  
  RESULTS
  Four hundred and twenty-one out of 3316(13%) patients reported preexisting peripheral neuropathy at ART initiation. Median (interquartile range, IQR) follow-up in 2895 participants without preexisting peripheral neuropathy was 4.9 (4.7-5.4) years. Three hundred and fifty-four (12%) took stavudine as first-line substitution and 518 (18%) took isoniazid during follow-up. Two hundred and ninety (11%) participants developed a new peripheral neuropathy episode, an incidence of 2.12 per 100 person-years. Eighteen (0.1%) had a grade 3/4 episode. Independent predictors of peripheral neuropathy were current stavudine use [adjusted hazard ratio (a)HR 4.16 (95% confidence interval, 95% CI 3.06-5.66], current isoniazid use [aHR 1.59 (95% CI 1.02-2.47)] and current didanosine use [aHR 1.60 (95% CI 1.19-2.14)]. Higher risks were independently associated with higher pre-ART weight [aHR (per+5 kg) 1.07 (95% CI 1.01-1.13)] and older age aHR (per 10 years older) 1.29 (95% CI 1.12-1.49), but there was no significant effect of sex (P = 0.13), pre-ART CD4(+) cell count (P = 0.91) or CD4(+) cell count monitoring (P = 0.73).
  
  
  CONCLUSIONS
  Current stavudine, didanosine or isoniazid use continue to increase peripheral neuropathy risks, as does older age and weight at ART initiation; however, we found no evidence of increased risk in women in contrast to previous studies. The incidence of peripheral neuropathy may now be lower in ART programmes, as stavudine and didanosine are no longer recommended. All patients receiving isoniazid, either as part of antituberculosis (TB) chemotherapy or TB-preventive therapy, should receive pyridoxine as recommended in national guidelines.
authors.affiliation: aMedical Research Council /UVRI, Entebbe bMakerere University, Infectious Diseases Institute cJoint Clinical Research Centre, Kampala, Uganda dUniversity of Zimbabwe, Harare, Zimbabwe eSchool of Population Health, University of Queensland, Brisbane, Queensland, Australia fMedical Research Council Clinical Trials Unit at University College London, London, UK.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Kiwuwa-Muyingo
authors.forename: Bernard
authors.initials: B
authors.lastname: Kikaire
authors.forename: Ivan
authors.initials: I
authors.lastname: Mambule
authors.forename: Helen
authors.initials: H
authors.lastname: Musana
authors.forename: Godfrey
authors.initials: G
authors.lastname: Musoro
authors.forename: Charles F
authors.initials: CF
authors.lastname: Gilks
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Levin
authors.forename: Anne Sarah
authors.initials: AS
authors.lastname: Walker
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000627:therapeutic use; D016049:Didanosine / Q000627:therapeutic use; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D015994:Incidence; D007538:Isoniazid / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010523:Peripheral Nervous System Diseases / Q000453:epidemiology*; D015995:Prevalence; D012307:Risk Factors; D018119:Stavudine / Q000627:therapeutic use; D014454:Uganda / Q000453:epidemiology; D055815:Young Adult; D015215:Zidovudine / Q000627:therapeutic use; D015030:Zimbabwe / Q000453:epidemiology
chemical_list: D044966:Anti-Retroviral Agents; D000995:Antitubercular Agents; D015215:Zidovudine; D018119:Stavudine; D016049:Didanosine; D007538:Isoniazid