Lack of association between stavudine exposure and lipoatrophy, dysglycaemia, hyperlactataemia and hypertriglyceridaemia: a prospective cross sectional study

Simple item page
dc.contributor.authorSinxadi, Phumlaen_ZA
dc.contributor.authorvan der Walt, Jan-Stefanen_ZA
dc.contributor.authorMcIlleron, Helenen_ZA
dc.contributor.authorBadri, Motasimen_ZA
dc.contributor.authorSmith, Peteren_ZA
dc.contributor.authorDave, Joelen_ZA
dc.contributor.authorLevitt, Naomien_ZA
dc.contributor.authorMaartens, Garyen_ZA
dc.date.accessioned2015-11-11T12:02:10Z
dc.date.available2015-11-11T12:02:10Z
dc.date.issued2010en_ZA
dc.description.abstractBACKGROUND: Stavudine continues to be widely used in resource poor settings despite its toxicity. Our objective was to determine association between plasma stavudine concentrations and lipoatrophy, concentrations of glucose, lactate and triglycerides. METHODS: Participants were enrolled in a cross-sectional study with lipoatrophy assessment, oral glucose tolerance test, fasting triglycerides, finger prick lactate, and stavudine concentrations. Individual predictions of the area under the concentration curve (AUC) were obtained using a population pharmacokinetic approach. Logistic regression models were fitted to assess the association between stavudine geometric mean ratio > 1 and impaired fasting glucose, impaired glucose tolerance, hyperlactataemia, hypertriglyceridaemia, and lipoatrophy. RESULTS: There were 47 study participants with a median age of 34 years and 83% were women. The median body mass index and waist:hip ratio was 24.5 kg/m2 and 0.85 respectively. The median duration on stavudine treatment was 14.5 months. The prevalence of lipoatrophy, impaired fasting glucose, impaired glucose tolerance, hyperlactataemia, and hypertriglyceridaemia were 34%, 19%, 4%, 32%, and 23% respectively. Estimated median (interquartile range) stavudine AUC was 2191 (1957 to 2712) ng*h/mL. Twenty two participants had stavudine geometric mean ratio >1. Univariate logistic regression analysis showed no association between stavudine geometric mean ratio >1 and impaired fasting glucose (odds ratio (OR) 2.00, 95% CI 0.44 to 9.19), impaired glucose tolerance (OR 1.14, 95% CI 0.07 to 19.42), hyperlactataemia (OR 2.19, 95%CI 0.63 to 7.66), hypertriglyceridaemia (OR 1.75, 95%CI 0.44 to 7.04), and lipoatrophy (OR 0.83, 95% CI 0.25 to 2.79). CONCLUSIONS: There was a high prevalence of metabolic complications of stavudine, but these were not associated with plasma stavudine concentrations. Until there is universal access to safer antiretroviral drugs, there is a need for further studies examining the pathogenesis of stavudine-associated toxicities.en_ZA
dc.identifier.apacitationSinxadi, P., van der Walt, J., McIlleron, H., Badri, M., Smith, P., Dave, J., ... Maartens, G. (2010). Lack of association between stavudine exposure and lipoatrophy, dysglycaemia, hyperlactataemia and hypertriglyceridaemia: a prospective cross sectional study. <i>AIDS Research and Therapy</i>, http://hdl.handle.net/11427/14893en_ZA
dc.identifier.chicagocitationSinxadi, Phumla, Jan-Stefan van der Walt, Helen McIlleron, Motasim Badri, Peter Smith, Joel Dave, Naomi Levitt, and Gary Maartens "Lack of association between stavudine exposure and lipoatrophy, dysglycaemia, hyperlactataemia and hypertriglyceridaemia: a prospective cross sectional study." <i>AIDS Research and Therapy</i> (2010) http://hdl.handle.net/11427/14893en_ZA
dc.identifier.citationSinxadi, P. Z., van der Walt, J. S., McIlleron, H. M., Badri, M., Smith, P. J., Dave, J. A., ... & Maartens, G. (2010). Lack of association between stavudine exposure and lipoatrophy, dysglycaemia, hyperlactataemia and hypertriglyceridaemia: a prospective cross sectional study. AIDS Res Ther, 7(1), 23.en_ZA
dc.identifier.ris TY - Journal Article AU - Sinxadi, Phumla AU - van der Walt, Jan-Stefan AU - McIlleron, Helen AU - Badri, Motasim AU - Smith, Peter AU - Dave, Joel AU - Levitt, Naomi AU - Maartens, Gary AB - BACKGROUND: Stavudine continues to be widely used in resource poor settings despite its toxicity. Our objective was to determine association between plasma stavudine concentrations and lipoatrophy, concentrations of glucose, lactate and triglycerides. METHODS: Participants were enrolled in a cross-sectional study with lipoatrophy assessment, oral glucose tolerance test, fasting triglycerides, finger prick lactate, and stavudine concentrations. Individual predictions of the area under the concentration curve (AUC) were obtained using a population pharmacokinetic approach. Logistic regression models were fitted to assess the association between stavudine geometric mean ratio > 1 and impaired fasting glucose, impaired glucose tolerance, hyperlactataemia, hypertriglyceridaemia, and lipoatrophy. RESULTS: There were 47 study participants with a median age of 34 years and 83% were women. The median body mass index and waist:hip ratio was 24.5 kg/m2 and 0.85 respectively. The median duration on stavudine treatment was 14.5 months. The prevalence of lipoatrophy, impaired fasting glucose, impaired glucose tolerance, hyperlactataemia, and hypertriglyceridaemia were 34%, 19%, 4%, 32%, and 23% respectively. Estimated median (interquartile range) stavudine AUC was 2191 (1957 to 2712) ng*h/mL. Twenty two participants had stavudine geometric mean ratio >1. Univariate logistic regression analysis showed no association between stavudine geometric mean ratio >1 and impaired fasting glucose (odds ratio (OR) 2.00, 95% CI 0.44 to 9.19), impaired glucose tolerance (OR 1.14, 95% CI 0.07 to 19.42), hyperlactataemia (OR 2.19, 95%CI 0.63 to 7.66), hypertriglyceridaemia (OR 1.75, 95%CI 0.44 to 7.04), and lipoatrophy (OR 0.83, 95% CI 0.25 to 2.79). CONCLUSIONS: There was a high prevalence of metabolic complications of stavudine, but these were not associated with plasma stavudine concentrations. Until there is universal access to safer antiretroviral drugs, there is a need for further studies examining the pathogenesis of stavudine-associated toxicities. DA - 2010 DB - OpenUCT DO - 10.1186/1742-6405-7-23 DP - University of Cape Town J1 - AIDS Research and Therapy LK - https://open.uct.ac.za PB - University of Cape Town PY - 2010 T1 - Lack of association between stavudine exposure and lipoatrophy, dysglycaemia, hyperlactataemia and hypertriglyceridaemia: a prospective cross sectional study TI - Lack of association between stavudine exposure and lipoatrophy, dysglycaemia, hyperlactataemia and hypertriglyceridaemia: a prospective cross sectional study UR - http://hdl.handle.net/11427/14893 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/14893
dc.identifier.urihttp://dx.doi.org/10.1186/1742-6405-7-23
dc.identifier.vancouvercitationSinxadi P, van der Walt J, McIlleron H, Badri M, Smith P, Dave J, et al. Lack of association between stavudine exposure and lipoatrophy, dysglycaemia, hyperlactataemia and hypertriglyceridaemia: a prospective cross sectional study. AIDS Research and Therapy. 2010; http://hdl.handle.net/11427/14893.en_ZA
dc.language.isoengen_ZA
dc.publisherBioMed Central Ltden_ZA
dc.publisher.departmentDivision of Clinical Pharmacologyen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution Licenseen_ZA
dc.rights.holder2010 Sinxadi et al; licensee BioMed Central Ltd.en_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/2.0en_ZA
dc.sourceAIDS Research and Therapyen_ZA
dc.source.urihttp://www.aidsrestherapy.com/en_ZA
dc.subject.otherPeripheral Fat Lossen_ZA
dc.subject.otherReverse Transcriptase Inhibitoren_ZA
dc.subject.otherGlucose Tolerance Testen_ZA
dc.subject.otherfixed Dose Combinationen_ZA
dc.subject.otherCurrent CD4 Counten_ZA
dc.subject.otherLactate Concentrationen_ZA
dc.subject.otherHIV-infected Adulten_ZA
dc.titleLack of association between stavudine exposure and lipoatrophy, dysglycaemia, hyperlactataemia and hypertriglyceridaemia: a prospective cross sectional studyen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Sinxadi_association_between_stavudine_exposure_2010.pdf
Size:
333.2 KB
Format:
Adobe Portable Document Format
Description:
Download
Collections
Journal Articles