Higher-than-expected rates of lactic acidosis among highly active antiretroviral therapy-treated women in Botswana: preliminary results from a large randomized clinical trial.

Higher-than-expected rates of lactic acidosis among highly active antiretroviral therapy-treated women in Botswana: preliminary results from a large randomized clinical trial.

MedLine Citation:	PMID: 18090299 Owner: NLM Status: MEDLINE
Abstract/OtherAbstract:	BACKGROUND: The ability of nucleoside reverse transcriptase inhibitors (NRTIs) to inhibit human mitochondrial polymerase-gamma results in impaired synthesis of mitochondrial enzymes that generate adenosine triphosphate (ATP) by oxidative phosphorylation. This has been associated with several long-term mitochondrial toxicities, which include lactic acidosis and pancreatitis, peripheral neuropathy, and lipoatrophy. METHODS: Enrolled highly active antiretroviral therapy (HAART)-treated adults have completed nearly 2 years of follow-up as part of the ongoing randomized clinical trial Adult Antiretroviral Treatment and Drug Resistance (Tshepo) study. All patients were intensively screened for the presence of ARV-related toxicities. RESULTS: Six hundred fifty adults (69% female) were initiated on NRTI-based HAART. Overall, 2.0% of patients developed moderate to severe symptomatic hyperlactatemia, with 7 (1.0%), all female, diagnosed with lactic acidosis. Female gender (P = 0.008) and being overweight, namely having a body mass index (BMI) of greater than 25 (P = 0.001), were predictive for the development of moderate to severe symptomatic hyperlactatemia or lactic acidosis. Older age (age >40 years) showed a statistical trend (P = 0.053) as a predictor for the development of toxicity, whereas exposure to d4T and/or ddI for 6 or more months was not predictive (P = 0.102). Those diagnosed with lactic acidosis had a mean BMI of 32.38 (interquartile range [IQR] = 29.4 to 35) at the time of toxicity and had been receiving HAART for a mean of 12.1 months (IQR = 7 to 20.8). Four of the 7 (57%) died of lactic acidosis and/or hemorrhagic pancreatitis; these 4 patients also had a comorbid diagnosis of severe clinical pancreatitis with grade 3/4 lipase elevations and abdominal symptoms at the time of their demise. CONCLUSIONS: Rates of lactic acidosis appear to be higher in southern Africa when compared with rates previously described elsewhere. Risk factors for the development of moderate to severe symptomatic hyperlactatemia or lactic acidosis appear to be multifactorial but include female gender and having a BMI of greater than 25. Additional studies are ongoing to evaluate for other possible risk factors, such as host genetic differences.

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
Related Documents :	17687599 - Prognostic factors in patients undergoing surgery for severe necrotizing pancreatitis. 23104609 - Intraoperative determinants of rotator cuff repair integrity: an analysis of 500 consec... 11593119 - Effects of therapy with lansoprazole on intestinal permeability and inflammation in you... 18607279 - Impact of upper gastrointestinal endoscopic ultrasound in children. 10875989 - The feasibility of spleen-preserving pancreatectomy for end-stage chronic pancreatitis. 15057739 - Prophylactic antibiotic treatment in patients with predicted severe acute pancreatitis:... 2277369 - Endometrial ablation with the roller ball electrode. 11164739 - Does the control of alanine aminotransferase levels lead to a regression of liver fibro... 22926749 - Single-legged hop tests as predictors of self-reported knee function after anterior cru...
Publication Detail:	Type: Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Journal Detail:	Title: Journal of acquired immune deficiency syndromes (1999) Volume: 46 ISSN: 1525-4135 ISO Abbreviation: J. Acquir. Immune Defic. Syndr. Publication Date: 2007 Nov
Date Detail:	Created Date: 2007-12-19 Completed Date: 2008-01-23 Revised Date: 2008-02-29
Medline Journal Info:	Nlm Unique ID: 100892005 Medline TA: J Acquir Immune Defic Syndr Country: United States
Other Details:	Languages: eng Pagination: 318-22 Citation Subset: IM; X
Affiliation:	Botswana-Harvard School of Public Health AIDS Initiative Partnership for HIV Research and Education, Gaborone, Botswana.
Export Citation:	APA/MLA Format Download EndNote Download BibTex
MeSH Terms
Descriptor/Qualifier:	Acidosis, Lactic / epidemiology* Acquired Immunodeficiency Syndrome / complications, drug therapy Adult Antiretroviral Therapy, Highly Active / adverse effects* Botswana CD4 Lymphocyte Count Female Humans Lactates / blood Middle Aged Patient Selection
Grant Support
ID/Acronym/Agency:	K23-AI073141/AI/NIAID NIH HHS; K24 RR16482/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:	0/Lactates

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document: Prevalence of HIV-2 and HIV-1 group O infections among new HIV diagnoses in France: 2003-2006.
Next Document: Reorganization of neural circuits in the blind on diffusion direction analysis.