D.Phil. / This enquiry represents an attempt to understand the ways in which the ecology of ideas surrounding HIV and Aids in post-apartheid South Africa functions discursively to silence people living with the dis-ease. In this regard, it seeks to understand how the range of subject positions available to people with HIV and Aids influences their opportunities for treatment and disclosure. The meanings emerging from this enquiry have implications for interventions aimed at people living with HIV and Aids, in that they challenge the liberal humanism underpinning a Western individualist paradigm which constructs people as ‘rational’ and ‘responsible’ on the basis that such constructions tend to attribute guilt or moral culpability to people living with HIV and Aids. The conversations and narratives elicited in the process of this enquiry suggest that such discourses constitute a form of disciplinary power in a Foucauldian sense, positioning people living with HIV and Aids defensively and limiting their options for ‘positive’ self-definition by foreclosing available subject positions, thereby contributing to the spread of HIV and Aids. Hence, this enquiry focuses on social constructions of morality and the impact of these on participants’ attempts to maintain key relationships that afford them a ‘positive’ sense of them-selves. Thus, it looks at experiences of connection and dis-connection and explores the ways in which efforts to retain ‘relatedness’ in order to maximise possibilities for the co-construction of a ‘moral self’ mediate opportunities for disclosure and treatment options. The enquiry aimed to assist participants in deconstructing dominant social constructions of HIV and Aids implicit in cultural and political discourse by applying a critical, poststructuralist and discourse-analytic lens in order that they might resist moral attributions based on liberal humanism and access their own voices in narrating the experience of living with HIV and Aids in keeping with their lived experience. My aim in this regard was to resurrect alternative or previously silenced accounts and to open up spaces for a multiplicity of meanings associated with HIV and Aids to emerge and be heard, toward the end of breaking the silence and creating a conversational space in which people’s meanings could simultaneously be heard and challenged through dialogue.Ultimately, this enquiry highlights the importance of attempting to understand the local and idiosyncratic nature of people’s constructions of HIV and Aids, which are often a hybrid mix of ideas and meanings circulating within social, cultural and political discourse. It also underscores the salience of considering people’s lives in context and particularly their need to maintain relationships that afford a positive sense of self. This is reflected in the tendency for participants to construct their identities in relation to significant others and for these relationships to mediate decision making in relation to HIV and Aids by availing or foreclosing certain subject positions, depending on the discourses within which they are situated.

M.Tech. / HIV/AIDS is one of the greatest and still unresolved challenges facing the world today (Giese, 2002). The UNAIDS (2004) Reports, 38 million people are infected globally with HIV/AIDS. One of the most devastating impacts of HIV/AIDS is the effect on children. Over 5 million infants have been infected with HIV/AIDS since the beginning of the epidemic and 90% of these cases are in Africa (Osborne, 2002). The aim of the study was to determine the effect of a combination of four homoeopathically prepared growth factors, compounded and named Cell Signal Enhancers®, on CD4% and CD4+ cell count, growth parameters such as weight, height and head circumference and clinical outcomes in children with HIV/AIDS. A sample of thirty-one (n=31) HIV positive children between one to thirteen years of age was recruited. Twenty-five (n=25) participants completed the trial. The participants were recruited from an informal squatter area called Finetown, situated south of Johannesburg. The parents or legal guardian of each participant were required to read and sign a Patient Information and Consent form (Appendix A). The duration of the study was fourteen weeks. Each participant acted as his/her own control in a two week pre-treament period. Analysis of CD4% and CD4+ cell count, measurements of growth parameters that included weight, height and head circumference and evaluation of the clinical outcomes were conducted pre-treatment, during treatment and post treatment. The school principal and daily caregiver administered the homoeopathic growth factor medication to each participant. One tablet was given three times a day, for a twelve week period. Statistical models such as a paired t-test, one-sample t-test and linear regression were used to analyse the data. The resultant analyses of the data have provided the following conclusions. HoGF treatment improved immune function of the participants, as there were increases in CD4% and CD4+ cell counts and an overall decrease in frequency of HIV symptoms. HoGF intervention reversed growth failure. This was demonstrated with increases in weight, height and head circumference that resulted in a form of “catch up” growth. When compared to published data trends of age-matched subjects using ART, HoGF demonstrated more favourable effects in the CD4%, CD4+ cell counts and growth parameters in a twelve week period. HoGF treatment was effective in each stage of HIV/AIDS; namely the asymptomatic, symptomatic and AIDS group. HoGF has proven to be effective in treating HIV infected children living with limited resources. It showed a 52% positive result as statistically significant versus a 5% prediction by random chance. Statistical significance was detected in the following; height, head circumference, energy, strength, vomiting, lymphadenopathy, skin lesions, respiratory tract infection, sinus tenderness and throat infection. There were no reported signs of adverse side effects while on HoGF treatment. The results of this study are expected to initiate further, much needed research in the area of HIV/AIDS and homoeopathy in both children and adults. It is recommended that future studies include a control group with placebo for inter-group comparisons. HoGF treatment can be seen as a possible public health option for treating HIV/AIDS in South Africa.

A thesis submitted to Faculty of Health Sciences, University of the Witwatersrand, in fulfillment of the requirements for the degree of Doctor of Philosophy Johannesburg, March 2014 / The ability to induce a broadly neutralizing antibody (bNAb) response following vaccination is regarded as a crucial aspect in developing an effective vaccine targeting the human immunodeficiency virus type 1 (HIV-1). The bNAbs target the HIV-1 envelope glycoprotein (Env) which is exposed on the surface of the virion, thereby preventing cell entry. Previous work in our laboratory focused on the generation of a 2dCD4S60C molecule (a variant of the CD4 primary Env receptor) with higher affinity for HIV-1 Env through targeted disulphide exchange. This study reports on the design and construction of an HIV-1 subtype C founder virus consensus Env immunogen derived from newly transmitted/founder virus sequences, and the ability of the purified recombinant Env proteins (2dCD4S60C-liganded and unliganded) to induce a broadly neutralizing antibody response in small animals. A total of 1894 founder sequences from 80 HIV-1 subtype C infected patients were available and downloaded from the databases. A consensus sequence was generated for each of the patients, and this alignment was subsequently used to generate a founder virus consensus env sequence. The env sequence was used to create codon-optimized constructs encoding monomeric (gp120FVCm), dimeric (gp120FVCGCN4d) and trimeric (gp140FVCGCN4t(+) and gp140FVCGCN4t(-) founder virus conformations cloned into the pcDNA3.1(-) mammalian expression vector. All four Env constructs were successfully expressed in HEK293T mammalian cell culture. The 2dCD4S60C was expressed in E. coli BL21 (DE3) and purified by nickel affinity chromatography. Large scale expression and purification of the gp120, gp120GCN4 and gp140GCN4 +/- in the unliganded or 2dCD4S60C liganded state were purified by lectin affinity chromatography, followed by conformation and complex purification using size exclusion chromatography. Immunogens/immune complexes were evaluated by ELISA, SDS-PAGE, native PAGE and surface plasmon resonance, and confirmed they were functional and conformationally intact. Immunogenicity of each conformation alone or complexed to 2dCD4S60C was evaluated in rabbits. Breadth and potency of the rabbit sera was tested against 12 pseudoviruses (Tiers 1-3), derived from HIV-1 subtype B and C Env, using the PhenoSense Neutralizing antibody assay (Monogram Bioscience, Inc.). Minimal neutralizing breadth was obtained from animals immunized exclusively with Env conformations. However, animals that received the Env/2dCD4S60C complex showed extensive neutralizing capacity against all 12 viruses tested, including the tier 2 and 3 virus strains. End-point ELISA titer results revealed that the rabbits that were immunized with Env/2dCD4S60C produced both Env and 2dCD4S60C specific titers, but those directed towards 2dCD4 were on average 10x lower than the 2dCD4S60C control group. This implies a proportion of the NAb activity is directed towards conserved epitopes exposed on the Env/2dCD4S60C immunogens. Overall, these results show that the use of founder Env/2dCD4S60C complexes as vaccine immunogens dramatically improves the antibody neutralization breadth and magnitude as compared to founder Env or 2dCD4S60C alone. This level of broad neutralization has not been previously reported in the literature, and these results provide encouraging data to inform us of the best envelope vaccine immunogen to include in a preventative vaccine.

No description available.

Indiana University-Purdue University Indianapolis (IUPUI) / HIV-1 infection is one of the greatest public health concerns today. The current HIV/AIDS therapy is effective in halting virus multiplication and has improved the outlook of AIDS; however, high cost, side effects, and the rise of drug-resistant viral strains have posed challenges for long-term treatment and management and mandate development of alternative anti-HIV therapies. Despite the fact that a great deal of progress has been made in our understanding of the infection over the last twenty-seven years, there are many unanswered basic scientific questions and no vaccines. In this study, we focused on two aspects related to the HIV-1 protein Nef: one is development of a Nef-based anti-HIV therapeutic strategy; the other is discovery of a novel mechanism that accounts for Nef-enhanced viral infectivity. We first devised an anti-HIV therapeutic strategy that took advantage of the high virion incorporation of the Nef mutant Nef7 to deliver anti-HIV factors to the virion. We performed a series of proof-of-concept experiments, using the host anti-HIV cellular factor APOBEC3G (A3G). The Nef7.A3G fusion protein retains important properties of Nef7: higher virion incorporation efficiency, lack of PAK2 activation, and reduced CD4 and MHC I downregulation, as well the anti-HIV infectivity function of A3G. Moreover, virus-like particle (VLP)-mediated delivery of Nef7.A3G into infected CD4+ T lymphocytes leads to inhibition of HIV-1 replication in these cells. These results support the use of Nef7 as an anti-HIV therapeutic strategy for the delivery of therapeutic proteins into HIV-1 virions. HIV-1 Nef protein has long been known to enhance viral infectivity. However, the underlying molecular mechanism remained elusive. Here we show that Nef is important for VS formation and VS-mediated virus transmission from cell to cell, especially in primary cells. Nef accomplishes this by inducing the clustering of VS components CD81 and ZAP70 and by inducing formation of actin protrusions, and these functions involve specific and distinct Nef domains. These findings not only yield new insights into the regulatory function of Nef in viral infectivity, but could also lead to development of more effective anti-HIV therapies that work equally well at blocking both VS-mediated and cell-free virus infection.

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfillment of the requirements for the degree of Masters of Medicine. Johannesburg 2019 / Background: The high level of co-morbid TB/HIV cases with severe organ failure on presentation in South Africa, results in an increased number of ICU admissions often with a poor prognosis at presentation. In this study, the aim was to identify patients admitted with HIV/TB co-infection and calculate the APACHE II scores and SOFA scores for each patient. Predicted percentage mortality was compared with actual mortality. Predictors of mortality were further identified, as well as the benefit of initiating ARV treatment in patients who are ARV naive upon admission to ICU. Methods: A retrospective audit of consecutive cases over a 24 month period was completed. Patient demographics; CD 4 count; ARV treatment status; ICU and 30 day mortality; the APACHE II Score; SOFA scores and correlating predicted percentage mortality were documented. The survival of patients was assessed using Kaplan Meier survival curves, and a univariate analysis was performed to identify risk factors for mortality. Calculated predicted mortality was compared with actual mortality to validate each scoring system and infer which was the better tool. Results: Of 75 patients admitted with pulmonary (43 cases) or extra-pulmonary (32 cases) TB, 23 died in the ICU (mortality 30,7%), and a further 10 died in the first 30 days of hospitalisation (30 day mortality 44%). A survival analysis established ARV treatment and CD 4 counts greater than 50 cells/mm3 were associated with a higher survival rate at any point of the analysis. In the entire study period, only 2 patients were initiated on ARV therapy during their ICU stay, 1 survived to discharge and 1 died in ICU. The APACHE II Predicted Mortality was within the 95% Confidence Intervals for all groups while the SOFA score was outside the upper bound limit of the 95% confidence intervals of actual mortality for those patients taking ARV treatment (52%, 95% CI 43,1% - 59,5% vs actual mortality 30%, 95% CI 17,7% - 46,1%), those with a CD 4 count of more than 50 (53,5% 95% CI 45,4% - 60,6% vs actual mortality 34%, 95% CI 22,1% - 48,4%) and female patients (51,2%, 95% CI 41,6% - 58,1% vs actual mortality 35,1%, 95% CI 21,4% - 50,4%). Conclusion: The study found that both the APACHE II and SOFA scoring systems were both statistically significant in prognosticating mortality in the study population. The APACHE II scoring system however showed a slightly improved prognostication in specific cohorts who had improved survival. It was also confirmed that patients with a CD 4 count of more than 50 cells/mm3, and those on ARV therapy had a statistically significant improved mortality. Further studies reviewing survival benefit of ARV initiation in ICU are warranted. ACKNOWLEDGEMENTS Supervisor: Prof GA Richards Co-Supervisor: Dr SHH Mohamadali Statistician: Mr MH Zondi Assistant - Data Collection: Ms S Madanlall / E.K. 2019

No description available.

Thesis (MSc)--Stellenbosch University, 2002. / ENGLISH ABSTRACT: Please see fulltext for abstract / AFRIKAANSE OPSOMMING: Sien asb volteks vir opsomming

Thesis (MComm (Statistics and Actuarial Science))--University of Stellenbosch, 2009. / Incidence can be defined as the rate of occurence of new infections of a disease like HIV and is an useful estimate of trends in the epidemic. Annualised incidence can be expressed as a proportion, namely the number of recent infections per year divided by the number of people at risk of infection. This number of recent infections is dependent on the window period, which is basically the period of time from seroconversion to being classified as a long-term infection for the first time. The BED capture enzyme immunoassay was developed to provide a way to distinguish between recent and long-term infections. An optical density (OD) measurement is obtained from this assay. Window period is defined as the number of days since seroconversion, with a baseline OD value of 0, 0476 to the number of days to reach an optical density of 0, 8.The aim of this study is to describe different techniques to estimate the window period which may subsequently lead to alternative estimates of annualised incidence of HIV infection. These various techniques are applied to different subsets of the Zimbabwe Vitamin A for Mothers and Babies (ZVITAMBO) dataset. Three different approaches are described to analyse window periods: a non-parametric survival analysis approach, the fitting of a general linear mixed model in a longitudinal data setting and a Bayesian approach of assigning probability distributions to the parameters of interest. These techniques are applied to different subsets and transformations of the data and the estimated mean and median window periods are obtained and utilised in the calculation of incidence.

<p>Curricula should be strengthened by teaching the curability of STIs and the importance of STI treatment to prevent HIV transmission. This study focused on the control of sexually transmitted infections as a key HIV prevention strategy. Sexually transmitted infections act as a strong cofactor in the sexual transmission of HIV. Effective STI management can limit the spread of HIV.</p>