Lactic acidosis in HIV-infected patients: a systematic review of published cases

Objective: To describe the clinical, epidemiological, and biochemical characteristics of published cases of lactic acidosis (LA) and to generate hypotheses concerning risk factors associated with this complication. Methods: Systematic review of cases reported in the medical literature. Results: 217 published cases were identified, 90 of which fulfilled the study definition and had sufficient individual data on potential risk factors to be included. The 90 patients had a mean age of 40.1 years (range 16–69) and 53% were female. All 90 patients were taking nucleoside reverse transcriptase inhibitors (NRTI) at the time of the episode. Among the 83 patients with details of their antiretroviral therapy (ART) regimen 51 patients were taking stavudine, 29 zidovudine, 27 didanosine, and 25 lamivudine. Around 50% of the patients had abdominal pain, nausea, or vomiting. Hepatic steatosis was consistently reported (53/90) and in 36 (68%) there was histological evidence. The case fatality rate was 48%. Six cases were rechallenged with NRTI and three developed a further LA episode. Using data on the numbers of HIV infected individuals receiving care in the United States, we estimate that the risk of LA could be 2.5 times higher for women than men. Conclusions: NRTI use and female sex appear to be risk factors for the development of LA. What other factors are involved is still not clear but might include duration of NRTI therapy, specific drug use, and genetic predisposition. A case-control study is needed to better define risk factors for severe LA.