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A novel controlled release intravaginal bioadhesive polymeric deviceNdesendo, , Valence Mathias Kessy 28 June 2010 (has links)
PhD Faculty of Health Sciences, University of the Witwatersrand, 2009. / HIV/AIDS was discovered almost a quarter of a century ago and has so far claimed the lives of
more than 25 million people worldwide. Developing countries remain disproportionately affected,
with sub-Saharan Africa contributing more than two-thirds of infections globally. Sexual
transmission is the primary route of HIV/AIDS acquisition, and women bear the greatest burden of
this pandemic. We are now at a stage where biotechnological advances are needed that can either
cure HIV/AIDS, stimulate the immune system to produce anti-HIV-antibodies by vaccination, or
prevent HIV infections. One of these advances has been the development of various microbicides.
However, a lack of effective drug delivery systems for these agents has remained as a rate-limiting
step towards successful HIV prevention. In an attempt to overcome this problem, this study aimed
at designing and developing a novel intravaginal bioadhesive polymeric device (IBPD) as a
delivery system to effectively deliver a microbicide {polystyrene sulfonate (PSS)} and antiretroviral
(ARV) {3'-azido-3'-deoxythymidine (AZT)} combination to the vagina. The development of a
successful intravaginal microbicidal drug delivery system requires the design of a formulation to
deliver the microbicide-ARV combination in a safe, effective, and consistent manner. The first step
therefore was to undertake extensive preliminary screening studies on various polymeric materials
using a one variable at a time (OVAT) approach to find suitable polymers for developing an IBPD.
Initially 18 biodegradable and biocompatible polymers were employed to produce 62 formulations
that were further screened through the OVAT approach to result in 15 lead formulations.
Two major concerns of this study were the attainment of satisfactory residence time of the IBPD in
the vagina as well as the ability of the IBPD to contain and release the microbicide-ARV in a
controlled manner. Therefore, optimization of the IBPD was based on these two requirements for
which proper matrix integrity was a pre-requisite. Artificial neural networks (ANNs), a computational
technique that is able to simulate the neurological processing ability of the human brain through
mathematical modeling, was employed for optimization. The ANN approach confirmed that 5 of the
18 studied polymers could be suitable for the development of an optimized IBPD. To finally attain
good vaginal retention for the developed delivery system, extensive bioadhesivity testing was
undertaken on the optimized device. Thorough in vitro and ex vivo bioadhesivity analysis was
conducted using physicomechanics and computational structural modeling. Allyl penta erythritolcrosslinked
poly acrylic acid (APE-PAA) appeared to contribute most to the bioadhesivity. Apart
from being employed as a matrix component, PAA was further used as a coating agent to achieve
extended bioadhesivity within the posterior fornix of the vagina. Since prolonged release and
suitable permeation of the microbicide-ARV across the vaginal tissue was a critical requirement of
this study, the device was designed to provide a controlled and prolonged drug release. Prolonged
release for up to 72 days was achieved. Furthermore, the design was constructed to ensure that
the released drug could permeate into the vaginal tissue and be retained substantially. This was
determined by measuring drug flux through ex-vivo permeation studies using freshly excised pig
vaginal tissue in a Franz Diffusion Cell (FDC) apparatus.
The ultimate aim of the study was to have the IBPD well accommodated in the vagina for
successful prevention of STIs and HIV infection. Achievement of this aim was ensured by
undertaking extensive in vivo studies in Large White pig model. The IBPDs were inserted under
anaesthesia into the posterior fornix of the vagina, using a novel applicator. To detect the retention
of the IBPDs and determine their sequential biodegradation pattern in the vagina, X-ray imaging
was employed, using radio-opaque Barium Sulphate (BaSO4). To demonstrate that the developed
drug delivery system acted locally and was only minimally absorbed systemically, blood samples
were taken from the jugular vein of each pig at pre-determined time intervals and subjected to
UPLC analysis. The drug content in the vaginal tissue at the end of the study was also determined.
Histopathological evaluation was carried out on vaginal epithelium to access the potential for
toxicity of the IBPDs. The drug content analysis revealed that greater amounts of AZT and PSS
were retained in the vaginal tissue with relatively small quantities (AZT:17%; PSS:13%) crossing
into the systemic circulation. The results from the toxicity studies showed that the IBPDs were safe
for use. This suggests that the developed drug delivery system (the IBPD) may be suitable for
application in the prevention of STIs and HIV infections.
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Analyzing how notions of masculinity influence the vulnerability of men to HIVMumbengegwi, Elizabeth January 2008 (has links)
Includes abstract.
Includes bibliographical references (leaves 77-84).
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The Public Sector HIV/AIDS Treatment Roll-out Campaign in the Western Cape: A case study highlighting success factors and challengesFuleihan, Nadia C January 2006 (has links)
Word processed copy. / Includes bibliographical references (leaves 84-98). / Until recently, the national implementation of a public sector Antiretroviral Therapy (ART) programme in South Africa seemed financially impossible. Drastically reduced prices for Antiretrovirals (ARVs) combined with substantial donor funding and the long-awaited adoption of a national treatment plan, have, however, shifted the debate. Now the question is not so much should universal ART be provided by government but, rather, is it possible to implement in severely resource-constrained environments and, if so, what are the best ways to deliver these services.
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Herstory : Maidei Chivi, an HIV positive Zimbabwean womanMphisa, Abigael January 2006 (has links)
Incudes bibliographical references. / The thesis is based on the story of a 36 year old HIV positive middle class black Zimbabwean woman, Maidei Chivi (pseudonym). Maidei is well educated, financially secure and wields enormous power both within her family and at her workplace. She therefore, unlike many women, does not fall into the typical HIV victim category, characterised by poverty, coerced sex and desperation. Maidei's story demonstrates that economic security does not necessarily result in women taking decision making roles during sex.
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Performance based funding from the Global Fund to fight AIDS, Tuberculosis and Malaria : a case study of Grant SAF-304-GO4-H in the Western Cape, South AfricaNaimak, Trude Holm January 2006 (has links)
Includes bibliographical references.
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Considering alternatives to the predomination model of volentary councelling and testing practiced in South AfricaBrown, Sean January 2009 (has links)
Testing is widely acknowledged to be a useful and necessary secondary tool of Human Immunodeficiency Virus (HIV) prevention. It is the method by which to identify people who are living with the virus, so that their behaviour may be modified and medical condition treated in order to prevent further infection. Unfortunately, many persons in South Africa (SA) remain undiagnosed and therefore unaware of their HIV-positive status. This thesis explores why it is necessary to test for HIV in SA, where the incidence of the virus remains the highest in the world. Voluntary Counselling and Testing (VCT) or the âopt-inâ approach has been adopted as the norm or âsine qua nonâ. The efficacy of this method will be interrogated and shortcomings identified. The most notable is that few people in SA undergo an HIV test in order to learn their status. When they do, it is often late in the progression of opportunistic infections, requiring hospitalisation that increases pressure on an already over-stretched healthcare system. Reasons for the poor uptake of VCT are explained, including pervasive stigma and deficiencies in leadership of SAâs HIV and AIDS response. The expansion of testing is a proposed response to the challenge of persons remaining undiagnosed, and includes the acceleration of âopt-outâ or routine HIV testing (RHT) among SAâs high prevalence population. This model offers an HIV test routinely to persons attending government healthcare settings with an illness or for a routine check-up. Although the provider initiates the test, consent is necessary in order to proceed and there is an option to decline. While the key focus of this thesis is routine HIV testing, other approaches are explored in brief, including mandatory testing, mobile clinics and wellness screening. The thesis argues that if SA is to achieve the HIV and AIDS and STI National Strategic Plan (NSP) target of increasing the number of adults who have ever had a test to 70 percent by 2011, new approaches to testing, and especially opt-out, will need to be explored and more widely adopted. Key words: HIV/AIDS; Voluntary Counselling and Testing (VCT); Routine HIV Testing (RHT); Routinely Recommended Testing (RRT); Opt-out Testing; Provider-Initiated Testing and Counselling (PITC).
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Responding to multi-dimensional forms of poverty in the context of HIV/AIDS: experiences of mothers in KhayelitshaKane, Dianna January 2008 (has links)
Includes abstract. / Includes bibliographical references (leaves 86-91). / South Africa is a highly unequal society, comprised of a small, wealthy elite class and a large population living in deep, chronic poverty plagued with unemployment. Those suffering from the greatest poverty are unemployed women caring for children. In the context of a distinct underclass that has been historically marginalized from the labour market and a welfare system does not provide assistance for the unemployed, these women are left to cope with their own poverty. Additionally, the HIV/AIDS epidemic exacerbates existing vulnerabilities and compromises the capabilities of these women and children. Guided by a livelihood framework and based on a multi-dimensional definition of poverty, the study explored how women navigate within their difficult environment to respond to the poverty of their children.
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Teaching the Life Skills curriculum : experiences of managing the blurred terrain of the public and private : an exploratory case study of women who teach 7th grade Life Skills on the Cape Flats of Cape Town, South AfricaMcCulla, Amy January 2007 (has links)
Word processed copy.
Includes bibliographical references (leaves 117-123).
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'They say you are not a man' : hegemonic masculinity and peer pressure amongst male adolescents in KwaZulu-Natal : implications for the HIV epidemicThomson, Hayley January 2009 (has links)
This study explores the links between masculinity and the spread of HIV/AIDS by examining adolescents’ conceptions of manhood and the ways in which hegemonic masculinity manifests itself through peer pressure. The study employed qualitative methods, including in-depth interviews and focus group discussions. Interviews were conducted with fifteen adolescent males between the ages of twelve to sixteen, who live in areas with high levels of HIV prevalence outside Pietermaritzburg in KwaZulu-Natal.
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Situating the HIV/AIDS epidemic in a historical context : a case study of orphans in Nguludi Mission Community, MalawiCroke, Rhian G January 2003 (has links)
Includes bibliography. / This thesis is based on a series of interviews with key informants and a census of orphan households in Nguludi Mission Community, Southern Malawi, in 2000. The thesis argues that although HIV/AIDS is a relatively recent phenomenon, any contemporary understanding of the epidemic must be informed by an understanding of the past. The impact of the HIV/AIDS epidemic and the "orphan problem" at the local level, is, therefore, situated within the broader socio-economic context of the history of the region.
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