title: Hyperlactataemia in HIV-infected patients: the role of NRTI-treatment.
abstract: BACKGROUND
  Long-term treatment with nucleoside reverse transcriptase inhibitors (NRTIs) can induce mitochondrial dysfunction, most severely represented by lactic acidosis. Diagnostic tests for mitochondrial dysfunction are lacking, although persistently elevated serum lactate might be a surrogate marker.
  
  
  OBJECTIVE
  To determine the occurrence of hyperlactataemia in HIV-infected patients on NRTI-treatment and to evaluate the possible risk factors.
  
  
  METHODS
  Cross-sectional analysis of lactic-acid levels in asymptomatic HIV-infected patients. Hyperlactactaemia was considered mild if between 2.0-5 mmol/l, serious if >5 mmol/l and lactic acidosis was defined as lactic acid levels >5 mmol/l with bicarbonate <20 mmol/l. Possible risk factors, such as current and preceding NRTI-treatment as well as treatment with non-nucleoside reverse transcriptase inhibitors or protease inhibitors and concurrent liver disease, were analysed.
  
  
  RESULTS
  Two hundred and twenty three asymptomatic HIV-infected patients were studied, including 174 patients (78%) on NRTI treatment, 12 patients (5%) treated without NRTIs and 37 patients (17%) not treated. Mild hyperlactataemia was found in 42 patients (19%), from whom 38/42 (90%) were NRTI-treated and the remaining patients (4/42, 10%) received no treatment (chi2, P<0.05). The significant risk factors for hyperlactataemia in the univariate analysis were NRTI-treatment as a group (P=0.03) and elevated ALT (P=0.008). In multivariate analysis NRTI use (P=0.05) and ALT level (P=0.03) remained a significant determinant of hyperlactataemia. Among the different individual NRTIs, a stavudine-containing (P=0.004) and a zalcitabine-containing (P=0.07) regimen were most notably associated with the development of hyperlactataemia, whereas for the combinations of NRTIs, such association was only found for stavudine/lamivudine (P=0.05).
  
  
  CONCLUSIONS
  A correlation between hyperlactataemia and NRTI treatment was found, but the value of routine lactate measurement for individual treatment monitoring remains uncertain.
authors.affiliation: Department of Internal Medicine, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands.
authors.forename: Saskia M E
authors.initials: SM
authors.lastname: Vrouenraets
authors.forename: Marco
authors.initials: M
authors.lastname: Treskes
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Regez
authors.forename: Nancy
authors.initials: N
authors.lastname: Troost
authors.forename: Yvo M
authors.initials: YM
authors.lastname: Smulders
authors.forename: Hugo M
authors.initials: HM
authors.lastname: Weigel
authors.forename: P H Jos
authors.initials: PH
authors.lastname: Frissen
authors.forename: Kees
authors.initials: K
authors.lastname: Brinkman
mesh_terms: D000140:Acidosis, Lactic / Q000139:chemically induced*; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects*; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D019344:Lactic Acid / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009705:Nucleosides / Q000009:adverse effects; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects*
chemical_list: D019380:Anti-HIV Agents; D009705:Nucleosides; D018894:Reverse Transcriptase Inhibitors; D019344:Lactic Acid