Risk Factors for Lactic Acidosis in HIV-Infected Patients Treated with Nucleoside Reverse-Transcriptase Inhibitors: A Case-Control Study

A case-control study was undertaken to determine risk factors for lactic acidosis in human immunodeficiancy virus-infected patients treated with nucleoside reverse-transcriptase inhibitors (NRTIs). From May 1996 to June 2000, 9 patients with lactic acidosis (defined as a plasma lactic acid level of >5 mM and plasma pH of <7.38) were identified. Control patients were randomly selected from among a large cohort of patients who initiated a dual NRTI regimen in 1996 or after. Two factors were associated with an increased risk of lactic acidosis: first, a creatinine clearance of <70 mL/min before lactic acidosis (OR, 15.8 [range, 3.0-86.5], P< 10-'), and, second, a low nadir CD4+ T lymphocyte count before the inception of NRTI therapy (OR, 8.4 [range, 1.2-cc], P = .03). The total cumulative exposure to NRTIs was not associated with an increased risk of lactic acidosis, nor was the cumulative exposure to any of the 4 NRTIs studied. According to these results, monitoring of creatinine clearance, especially in patients with a low nadir CD4' T lymphocyte count, could lead to modifications in antiretroviral therapy in order to diminish the risk of occurrence of lactic acidosis.