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    Stavudine induced lactic acidosis, risk factors and predictive laboratory markers : a nested case-control study in South Africa.

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    Date
    2012
    Author
    Luke, Christopher Alan.
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    Abstract
    Introduction The incidence of antiretroviral therapy induced lactic acidosis and its associated mortality may be reduced by appropriate dosing, risk stratification and early detection. This study describes the epidemiology, risk factors and predictive laboratory markers for lactic acidosis in subjects commenced on stavudine containing antiretroviral therapy between 2004 and 2007 at a hospital in KwaZulu- Natal. Persons with body weight above 60kg received 40mg twice daily and those below 30mg. Methods A nested case-control study design was used. Risk factor analysis was adjusted for the established risk factors of weight and gender. Results Lactic acidosis occurred in 79 (17 per 1000 person years) of 1 762 persons. Significant baseline risk factors were female gender (Adjusted Odds Ratio (AOR) =5.4) and increased body weight (AOR, compared to persons <60 kg, was 6.6 for persons 60 to 69 kg, 6.9 for persons 71 to 80 kg, and 95.7 for persons >80 kg). Predictors six months into therapy were an alanine transaminase >50 IU /L (AOR=11.1) and triglyceride between 1-1.5 mmol/l (AOR=11.2 compared to persons with triglyceride <0.5 mmol/l). No associations were found with regard to age, CD4 counts, viral loads or creatinine and albumin levels. Conclusion Obese females are at greatest risk for lactic acidosis with exponential increased in risk at weights above 80kg. The 30mg dose may be preferable, given that a sharp increase in risk occurred at 60kg, and that that the 30mg dose has been shown to have adequate virologic suppression. Additional risk factors for LA include an increase in alanine transaminase and triglyceride at 6 months of treatment.
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    http://hdl.handle.net/10413/11812
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