Higher-Than-Expected Rates of Lactic Acidosis Among Highly Active Antiretroviral Therapy-Treated Women in Botswana

• DOI: 10.1097/qai.0b013e3181568e3f
• Publication Date: 2009-03-03T22:04:46Z
• Authors: C William Wester; Okechukwu A Okezie; Ann Muir Thomas; Hermann Bussmann; Sikhulile Moyo; Tanaka Muzenda; Joseph Makhema; Erik van Widenfelt; Rosemary Musonda; Vladimir Novitsky; Tendani Gaolathe; Ndwapi Ndwapi; Max Essex; Daniel R Kuritzkes; Victor deGruttola; Richard G Marlink
• Keywords: Lactic acidosis; Mitochondrial toxicity; Hyperlactatemia; Interquartile range; Stavudine

Background: The ability of nucleoside reverse transcriptase inhibitors (NRTIs) to inhibit human mitochondrial polymerase-γ results in impaired synthesis enzymes that generate adenosine triphosphate (ATP) by oxidative phosphorylation. This has been associated with several long-term toxicities, which include lactic acidosis and pancreatitis, peripheral neuropathy, lipoatrophy. Methods: Enrolled highly active antiretroviral therapy (HAART)-treated adults have completed nearly 2 years follow-up as part the ongoing randomized clinical trial Adult Antiretroviral Treatment Drug Resistance (Tshepo) study. All patients were intensively screened for presence ARV-related toxicities. Results: Six hundred fifty (69% female) initiated on NRTI-based HAART. Overall, 2.0% developed moderate severe symptomatic hyperlactatemia, 7 (1.0%), all female, diagnosed acidosis. Female gender (P = 0.008) being overweight, namely having a body mass index (BMI) greater than 25 0.001), predictive development hyperlactatemia or Older age (age >40 years) showed statistical trend 0.053) predictor toxicity, whereas exposure d4T and/or ddI 6 more months was not 0.102). Those had mean BMI 32.38 (interquartile range [IQR] 29.4 35) at time toxicity receiving HAART 12.1 (IQR 20.8). Four (57%) died hemorrhagic pancreatitis; these 4 also comorbid diagnosis pancreatitis grade 3/4 lipase elevations abdominal symptoms their demise. Conclusions: Rates appear be higher southern Africa when compared rates previously described elsewhere. Risk factors multifactorial but female 25. Additional studies are evaluate other possible risk factors, such host genetic differences.