title: Severe hyperlactataemia complicating stavudine first-line antiretroviral therapy in South Africa.
abstract: BACKGROUND
  In the public sector antiretroviral therapy (ART) programme in South Africa the standardized first-line regimen includes stavudine (d4T). Severe symptomatic hyperlactataemia (SHL) is a potentially life-threatening complication of d4T.
  
  
  METHODS
  GF Jooste Hospital is a referral centre for six ART clinics. We retrospectively reviewed cases referred with lactate levels > or =5 mmol/l that were attributed to nucleoside reverse transcriptase inhibitors from August 2003 to November 2005. We calculated cumulative ART exposure in patients attending these clinics to derive a referral rate.
  
  
  RESULTS
  In total, 75 patients were referred with severe SHL (71 female). All had been on d4T and on ART for a median of 10 months. The referral rate for severe SHL was 17.5 cases per 1,000 patient-years. In 53 patients (71%), lactic acidosis (standard bicarbonate [SHCO3] <20 mmol/l) was confirmed, resulting in a referral rate of 12.3 cases per 1,000 patient-years. Twelve patients (16%) died during acute admission (< or =30 days). SHCO3 <15 mmol/l and pH < 7.2 were the only factors associated with acute mortality (odds ratio [OR] 22.5, 95% confidence interval [CI] 2.8-1,045.7 and OR 13.9, 95% CI 2.7-86.9, respectively). A total of 30 less severe cases were rechallenged with zidovudine without recurrence of SHL.
  
  
  CONCLUSIONS
  This study confirms a high incidence of severe SHL in Africa, which has been shown in previous studies. Rechallenge with zidovudine in less severe cases was found to be safe.
authors.affiliation: GF Jooste Hospital, Cape Town, South Africa. davestead@mweb.co.za
authors.forename: David
authors.initials: D
authors.lastname: Stead
authors.forename: Meg
authors.initials: M
authors.lastname: Osler
authors.forename: Andrew
authors.initials: A
authors.lastname: Boulle
authors.forename: Kevin
authors.initials: K
authors.lastname: Rebe
authors.forename: Graeme
authors.initials: G
authors.lastname: Meintjes
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D015994:Incidence; D007773:Lactates / Q000097:blood*; D008297:Male; D008875:Middle Aged; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D012720:Severity of Illness Index; D013019:South Africa; D018119:Stavudine / Q000008:administration & dosage / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D007773:Lactates; D018894:Reverse Transcriptase Inhibitors; D018119:Stavudine