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1. Innes, Steven Eugene Vere. Lipoatrophy in HIV-infected children on antiretroviral therapy.
Degree: PhD, Paediatrics and Child Health, 2013, Stellenbosch University
ENGLISH ABSTRACT: Introduction: Lipoatrophy is a common adverse effect of stavudine and this effect is strongly dose-dependent. Stavudine remains the most commonly used paediatric antiretroviral drug in sub-Saharan Africa, yet when the current study began in 2009, the prevalence and severity of lipoatrophy in children on antiretroviral therapy in sub-Saharan Africa had never been studied. The development of lipoatrophy may have serious and far-reaching consequences for patients and their families. The off-label stavudine dosing method, prescribed to children whose caregivers do not have access to a refrigerator, in which the contents of an adult capsule is mixed into tap water, has potential for over-dosing or under-dosing. In addition, children on stavudine continue to be exposed to a disproportionately high dose out of line with the reduced adult dose. Aims: 1. a) To investigate the prevalence and risk factors for lipoatrophy in HIV-infected children in Southern Africa b) To identify a simple anthropometric screening tool to detect early lipoatrophy in children 2. To validate the off-label stavudine dosing method prescribed to children whose caregivers do not have access to a refrigerator, with a view to reducing the recommended dose and thereby the side-effects. Methods: 1. a) We recruited pre-pubertal children on antiretroviral therapy from a family HIV clinic in our facility. Lipoatrophy was identified by two experienced paediatric HIV clinicians using a standardized grading scale. A dietician performed dietary assessment and anthropometric measurements. Previous antiretroviral exposures were recorded. A subset of recruits received Dual-Energy X-ray Absorbtiometry scanning. b) Anthropometric measurements in children with and without lipoatrophy were compared using multivariate linear regression adjusting for age and gender. The most discerning anthropometric variables underwent Receiver Operating Characteristic curve analysis to identify the most appropriate diagnostic cut-off. 2. a) Accuracy of the standard off-label stavudine dosing method was investigated using high-performance liquid chromatography to recover active drug from solutions made up using the prescribed method. This was compared to the stated drug content of the capsules. b) Bioavailability was investigated by performing a randomized crossover pharmacokinetic study wherein healthy HIV-seronegative adult volunteers received one of two generic stavudine capsule formulations, either intact or mixed in water using the prescribed method. Plasma stavudine concentrations were assayed by liquid chromatography tandem mass spectrometry. Results: 1. a) Prevalence of lipoatrophy was 36%, and incidence was 12% per person-year. Adjusted odds ratio for developing lipoatrophy was 1.9 (CI: 1.3–2.9) for each additional year of accumulated exposure to standard-dose stavudine. b) Baseline biceps skin-fold thickness correlated well with maximum lipoatrophy grading score at any site, giving a partial correlation coefficient of 0.33…Advisors/Committee Members: Cotton, Mark Fredric, Rosenkranz, Bernd, Rabie, Helena, Zollner, Ekkehard Werner, Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Paediatrics and Child Health..
Subjects/Keywords: Pediatrics; Dissertations – Pediatrics; Lipoatrophy – HIV-positive children – Risk factors; HIV positive children – Treatment; Antiretroviral agents – Risk factors; Stavudine – Therapeutic use; Pediatrics and Child Health
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APA (6th Edition):
Innes, S. E. V. (2013). Lipoatrophy in HIV-infected children on antiretroviral therapy. (Doctoral Dissertation). Stellenbosch University. Retrieved from http://hdl.handle.net/10019.1/79864
Chicago Manual of Style (16th Edition):
Innes, Steven Eugene Vere. “Lipoatrophy in HIV-infected children on antiretroviral therapy.” 2013. Doctoral Dissertation, Stellenbosch University. Accessed April 18, 2021. http://hdl.handle.net/10019.1/79864.
MLA Handbook (7th Edition):
Innes, Steven Eugene Vere. “Lipoatrophy in HIV-infected children on antiretroviral therapy.” 2013. Web. 18 Apr 2021.
Innes SEV. Lipoatrophy in HIV-infected children on antiretroviral therapy. [Internet] [Doctoral dissertation]. Stellenbosch University; 2013. [cited 2021 Apr 18]. Available from: http://hdl.handle.net/10019.1/79864.
Council of Science Editors:
Innes SEV. Lipoatrophy in HIV-infected children on antiretroviral therapy. [Doctoral Dissertation]. Stellenbosch University; 2013. Available from: http://hdl.handle.net/10019.1/79864