Lactic Acidosis; Risk Factors and Predictive Laboratory Markers: a Nested Case Control Study in South Africa

ABSTRACT

Background: The incidence of antiretroviral therapy (ART)-induced lactic acidosis and its associated mortality may be reduced by appropriate dosing; risk stratification and early detection. Objectives: To describe the epidemiology of lactic acidosis; define the risk factors and identify predictive laboratory markers in the context of the roll-out of ART in South Africa. Design: A nested case control study. Risk factor analysis was adjusted for the established risk factors of weight and gender.Setting and subjects: Persons commenced on stavudine-containing therapy between 2004 and 2007 at Port Shepstone Hospital in KwaZulu-Natal were included. Persons with a body weight above 60 kg received Stavudine 40 mg twice daily; and those with a body weight below 60 kg; 30 mg twice daily.Outcome measures: Assessed risk factors included weight; gender; age; alanine transaminase (ALT); urea; creatinine; albumin; cholesterol; triglyceride (TG) levels; CD4 counts and viral loads.Results: Lactic acidosis occurred in 79 (17 per 1 000 person-years) of 1 762 people living with HIV on ART. Significant factors were being female [adjusted odds ratio (AOR) of 5.4] and increased body weight (adjusted OR of 1.1 per kg). The risk of lactic acidosis increased 6.6; 6.9 and 95 times (adjusted ORs) as weight increased from a baseline weight of 60 kg to 60-69 kg; 70-79 kg or 80 kg; respectively. Six months into therapy; predictors of developing lactic acidosis were an ALT 50 IU/l (adjusted OR of 11.1) and a higher TG (adjusted OR of 8.8 per mmol/l). No associations were found with regard to age; CD4 count; viral load; and creatinine or albumin levels.Conclusion: Obese females are at greatest risk of lactic acidosis; with an exponential increase in risk above 80 kg. The 30-mg dose may be preferable; given that a sharp increase in risk occurred at 60 kg; was most likely dose related; and that 30 mg has been shown to provide adequate virological suppression. Additional risk factors for lactic acidosis include a high ALT and TG levels at treatment