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Modelling longitudinally measured outcome HIV biomarkers with immuno genetic parameters.Bryan, Susan Ruth. January 2011 (has links)
According to the Joint United Nations Programme against HIV/AIDS 2009 AIDS epidemic update, there were a total of 33.3 million (31.4 million–35.3 million) people living with HIV worldwide in 2009. The majority of the epidemic occurs in Sub-Saharan Africa. Of the 33.3 million people living with HIV worldwide in 2009, a vast majority of 22.5 million (20.9 million-24.2 million) were from Sub-Saharan Africa. There were 1.8 million (1.6 million-2.0 million) new infections and 1.3 million (1.1 million-1.5 million) AIDS-related deaths in Sub-Saharan Africa in 2009 (UNAIDS, 2009).
Statistical models and analysis are required in order to further understand the dynamics of HIV/AIDS and in the design of intervention and control strategies. Despite the prevalence of this disease, its pathogenesis is still poorly understood. A thorough understanding of HIV and factors that influence progression of the disease is required in order to prevent the further spread of the virus. Modelling provides us with a means to understand and predict the progression of the disease better.
Certain genetic factors play a key role in the way the disease progresses in a human body. For example HLA-B types and IL-10 genotypes are some of the genetic factors that have been independently associated with the control of HIV infection. Both HLA-B and IL-10 may influence the quality and magnitude of immune responses and IL-10 has also been shown to down regulate the expression of certain HLA molecules. Studies are therefore required to investigate how HLA-B types and IL-10 genotypes may interact to affect HIV infection outcomes.
This dissertation uses the Sinikithemba study data from the HIV Pathogenesis Programme (HPP) at the Medical School, University of KwaZulu-Natal involving 450 HIV positive and treatment naive individuals to model how certain outcome biomarkers (CD4+ counts and viral loads) are associated with immuno genetic parameters (HLA-B types and IL-10 genotypes). The work also seeks to exploit novel longitudinal data methods in Statistics in order to efficiently model longitudinally measured HIV
outcome data. Statistical techniques such as linear mixed models and generalized estimating equations were used to model this data. The findings from the current work agree quite closely with what is expected from the biological understanding of the disease. / Thesis (M.Sc.)-University of KwaZulu-Natal, Pietermaritzburg, 2011.
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The value of participatory and non-participatory implementation and evaluation methodologies of HIV/AIDS communication-based interventions in southern Africa.Niba, Mercy Bi. January 2004 (has links)
HIV/AIDS is an epidemic that is in one way or another affecting humankind and particularly the African continent. Due to its devastating nature, many strategies and interventions are being employed at different levels and by different groups of people to fight it. Evaluation has been a component of these projects, but few have been subjected to systematic monitoring and evaluation that provides a foundation for the development and implementation of further projects. This is partly due to the fact that project implementation and evaluation can be rendered complex by several factors, such as the choice of methodologies, donor satisfaction and the very nature of interventions and evaluations themselves. Taking a situation where the aim of a project and its evaluation is to bring about social change, as is the case with many HIV/AIDS interventions, this study sought to investigate approaches that could be considered meaningful, useful and valuable. In order to carry out the investigation of this study, the approach taken was an in-depth analysis of a few cases (in anticipation of greater achievement of insight), rather than broader survey types of perspectives. The study also concentrated on a review of the literature and on validation of documentary and interview evidence provided by beneficiaries, managerial staff and evaluators of communication-based HIV/AIDS. Results of the study highlighted the fact that community-based factors, such as education, poverty, culture, beliefs, gender, crime and age, influenced social change (with respect to HIV/AIDS) in varying ways and depending on the communities concerned. The different ways in which these factors influenced social change within specific communities were noted to have implications on interventions dealing with them. As such, an in-depth assessment of these different ways with respect to specific groups of people was encouraged in order to have a meaningful, useful and valuable HIV/AIDS intervention. The theory of active participation of targeted communities was also propagated in an HIV/AIDS intervention. It was noted that when active participation is encouraged in a project at both implementation and evaluation, taking the example of an HIV/AIDS project that intended achieving group knowledge acquisition, awareness, attitude change, skills acquisition, effective functioning and sustainability, such participation would contribute to: • Override to a great extent, limitations arising from socio-demographic differences (project locations and gender, language, age and race of implementers, evaluators and beneficiaries), in the attainment of project objectives. • Override to a great extent, limitations arising from differences in forms of evaluation (internal versus external evaluators), in the assessment of project objectives. • Create an enabling environment for higher attainment of project objectives in comparison to a situation where active participation is encouraged only at implementation (and not at evaluation). It was further discovered from this study that when beneficiaries are excluded from participating in the planning, action-planning and result-feedback stages of a project and its evaluation, dissatisfaction is experienced on the part of these beneficiaries as well as missed opportunities for useful contributions. The degree and quality of beneficiary involvement in project implementation and evaluation was seen to generate beneficiary excitement and a general sense of project acceptance: all of which was noted to create an enabling environment for the making of proper choices and decisions. Finally, difficulty in accessing traditional evaluations and people's feeling of shame and ineffectiveness was noted in the work (in the area of collecting data pertaining to traditional evaluation). This pointed to possible compromise of meaningfulness, usefulness and value of traditional evaluations. / Thesis (Ph.D.)-University of KwaZulu-Natal, Pietermaritzburg, 2004.
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Male prostitution and HIV/AIDS in Durban.Oosthuizen, A. H. J. January 2000 (has links)
This thesis sets out to describe and discuss male street prostitution as it occurs in
Durban. The aim is to examine to what degree male street prostitutes are at risk of HIV
infection, and make appropriate recommendations for HIV intervention.
The field data, gathered through participant observation, revealed significant differences
between the two research sites, refiecting broader race and class divisions in the South
African society. At the same time, the in-depth case studies of the individual participants
suggest that they share similar socio-economic life histories characterised by poverty
and dysfunctional families, and hold similar world-views.
The research was conducted within a social constructionist framework, guided by
theories of human sexuality. Yet, sexuality was not the framework within which the male
street prostitutes in Durban attached meaning to their profession. Professing to be
largely heterosexual, the respondents engaged in homosexual sexual acts without
considering themselves to be homosexual, reflecting and amplifying the fluid nature of
human sexuality. It was, however, within an economic framework that the male street
prostitutes who participated in this study understood and interpreted their profession.
The sexual aspect of their activities was far less important than the economic gain to
them, and prostitution was interpreted as a survival strategy,
A significant finding of this research is that male street prostitutes in Durban face a
considerably higher risk of exposure to HIV from their non-paying sexual partners
(lovers) than from their paying sex partners (clients). The research participants all had a
good knowledge of HIV and the potential danger of transmission whilst engaging in
unsafe commercial sex. In their private love lives, the participants were less cautious
about exposing themselves and their partners to HIV infection, hence the conclusion
that the respondents face a greater threat of HIV infection from their lovers than from
their clients.
Finally, male street prostitutes, like female street prostitutes, do however face some risk
of HIV infection as a result of their involvement with commercial sex. The illegal nature
of their activities is considered to contribute to an environment conducive to the
transmission of HIV, and this thesis argues for a change in the legal status of
commercial sex work as a primary component of HIV intervention in this vulnerable
group of men and women. / Thesis (M.A.)-University of Natal, Durban, 2000.
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CD4? T-cell deficiency and dysfunction in HIV patients receiving combination antiretroviral therapyFernandez, Sonia January 2007 (has links)
[Truncated abstract] Failure to fully reconstitute the immune system is a common clinical problem in HIV patients who were severely immunodeficient before responding to combination antiretroviral therapy (CART). This can manifest as a deficiency in the number or function of CD4+ T-cells and occurs most often in patients who had a nadir CD4+ T-cell count below 100/μl when CART was commenced. Observational studies of large cohorts of HIV patients, such as the D:A:D study, have demonstrated that patients with low CD4+ T-cell counts have increased rates of death compared with patients who have normal CD4+ T-cell counts. Furthermore, individual case studies suggest that impaired recovery of pathogen-specific immune responses during CART is associated with opportunistic infections or disease progression. This thesis addresses possible causes of deficiencies in CD4+ T-cell number or function in HIV patients who were very immunodeficient prior to treatment and are responding (virologically) to CART. Firstly, the role of the thymus in producing naive CD4+ T-cells and the effects of persistent immune activation on the recovery of CD4+ T-cell numbers were assessed in patients with either low or high CD4+ T-cell counts after long-term CART. ... Proportions of antigen presenting cell (APC) subpopulations were examined in HIV patients with low or high CMV-specific CD4+ T-cell responses after long-term CART. HIV patients had significantly lower proportions of plasmacytoid dendritic cells (pDC) than HIV-negative controls. Furthermore, the proportions of pDC were positively correlated with CMV-specific CD4+ T-cell responses in HIV patients. Proportions of myeloid dendritic cells (mDC) were significantly higher in HIV patients than controls, and were also increased in patients with low CMV-specific CD4+ T-cell responses. Proportions of M-DC8+ dendritic cells or CD14+ monocytes did not differ between patients and controls, nor were they associated with CMV-specific CD4+ T-cell responses. Quantitation of cytokine (interferon-α, tumour necrosis factor-α, interleukin (IL) -12, IL-23, IL-15, IL-18 and IL-10) mRNA in unstimulated, purified populations of the APC described above revealed few significant differences between patients with low or high CD4+ T-cell IFN-γ responses to CMV. The only notable difference was the slight elevation of IL-15 mRNA levels in patients compared to controls. Since patients in the high responder group had the highest levels of IL-15 mRNA, this association may reflect the anti-apoptotic properties of IL-15. These studies provide valuable insights into the causes of persistent CD4+ T-cell deficiency and dysfunction in HIV patients on CART and may lead to better monitoring and treatments.
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Immune activation during HIV-1 infection : implication for B cell dysfunctions and therapy monitoring /De Milito, Angelo, January 2002 (has links)
Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 6 uppsatser.
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The application of latent variable models to the assessment of determinants of HIV risk behavior /Smolenski, Derek Joseph. Risser, Jan Mary Hale, Stigler, Melissa H., Diamond, Pamela M. January 2009 (has links)
Thesis (Ph. D.)--University of Texas Health Science Center at Houston, School of Public Health, 2009. / Advisor: Michael W. Ross. Includes bibliographical references.
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Adherence to HIV/AIDS therapies among low-literacy populations : the ALP project /Fourney, Andrew Michael. Leonard, Lori. Kelder, Steven H. January 1999 (has links)
Thesis (Dr.P.H.)--University of Texas Health Science Center at Houston, School of Public Health, 1999. / Includes bibliographical references (leaves 127-136).
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The impact of AIDS education on seventh and eighth grade adolescents' knowledge, attitudes and beliefs about AIDS /Twomey, Creina, January 1996 (has links)
Thesis (M.N.)--Memorial University of Newfoundland, 1996. / Typescript. Bibliography: leaves 94-104. Also available online.
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L'expansion du VIH/Sida au Burkina Faso : perspective historique /Banhoro, Yacouba. January 1900 (has links)
Thesis (doctoral)--Universität, Hamburg, 2005. / Includes bibliographical references (p. 329-353).
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Molecular genetic analysis of human immunodeficiency virus antiretroviral therapy response in South Africa : a pharmacogenetics studyParathyras, John Burns 03 1900 (has links)
Thesis (MSc (Genetics))--University of Stellenbosch, 2007. / The results of pharmacotherapy can vary both within and between different populations and ethnic groups. Although numerous factors are believed responsible for observed discrepancies in drug response, genetic differences, most often in the form of single nucleotide polymorphisms (SNPs), between individuals and ethnic groups are an important and at times predominant factor. The response to antiretroviral (ARV) drugs for the treatment of human immunodeficiency virus (HIV)-infection is not dissimilar. Marked variations in both ARV efficacy and occurrence of adverse drug reactions (ADRs) have been observed on both an individual and ethnic group level, which are largely attributed to polymorphisms within genes involved in the metabolism and transport of these compounds – such genes include the CYP2B6 and CYP3A4 genes, both members of the cytochrome P450 (CYP) gene superfamily, and the multidrug-resistance 1 (MDR1) gene encoding an efflux transporter protein, phosphoglycoprotein (PGP).
An improved understanding of the genetic influences on ARV drug response could lead to improved therapies with fewer side-effects and minimised drug resistance. The main aim of this study was thus to investigate the genetic basis of observed differences in ARV therapy (ART) response in South African ethnic groups.
Deoxyribonucleic acid (DNA) samples were collected from 206 HIV-positive individuals of Mixed-Ancestry and Xhosa ethnicity that were currently or prospectively receiving ART. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was employed to screen the A-392G SNP in CYP3A4, the G516T and A785G SNPs in CYP2B6, and the T-129C, C1236T, G2677T/A and C3435T SNPs in MDR1. Hardy-Weinberg equilibrium (HWE) and haplotype analyses were subsequently performed on the resultant SNP genotype and ...
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