Philosophiae Doctor - PhD / There is a growing interest in the dynamics of the co-infection of these two diseases. In this thesis, firstly we focus on studying the effect of a distributed delay representing the incubation period for the malaria parasite in the mosquito vector to possibly reduce the initial transmission and prevalence of malaria. This model can be regarded as a generalization of SEI models (with a class for the latently infected mosquitoes) and SI models with a discrete delay for the incubation period in mosquitoes. We study the possibility of occurrence of backward bifurcation. We then extend these ideas to study a full model of HIV and malaria co-infection. To get further inside into the dynamics of the model, we use the geometric singular perturbation theory to couple the fast and slow models from the full model. Finally, since the governing models are very complex, they cannot be solved analytically and hence we develop and analyze a special class of numerical methods to solve them. / South Africa

Magister Administrationis - MAdmin / The main purpose of the study was to assess and explore the knowledge of HIV/AIDS among secondary learners in rural Bergville district of KwaZulu-Natal. A stratified random sample of 100 learners was selected from two secondary schools in the area. Data was collected using a questionnaire and interviews were scheduled with the teachers from the selected schools. The questionnaire was administered to a sample of 54 learners from school A and 46 from school B. The mean age was 16, with age range from 13-20. The participants were enrolled for grade 8-12 in both schools. Both qualitative and quantitative data on learners‟ knowledge and perception about HIV/AIDS, condom use and sexual issues including their attitudes towards people living with HIV/AIDS were collected in the questionnaire. Chi-square test was used for statistics purpose to test if the HIV knowledge of learners were associated with gender, culture and religion. Qualitative interviews with 9 teachers from both schools were conducted. The main purpose of the interviews was to investigate the management of HIV/AIDS in public schools in rural areas. Furthermore, to assess the learner‟s attitude towards HIV/AIDS education provided in schools. The results showed that the learners in Bergville district were more knowledgeable of HIV/AIDS through HIV/AIDS education in schools that had limited effect on gender, culture and religion. Quantitative findings presented, indicated no significant differences between those learners attending church and cultural activities that offer HIV/AIDS awareness programmes and those who do not with regard to the knowledge of HIV/AIDS. However, culture stood out to be associated with one item on the knowledge of whether school children can get HIV/AIDS (p-value = 0.04). On average, the level of knowledge of HIV/AIDS between female and male learners was similar. The major findings on both quantitative and qualitative findings confirmed that learners‟ knowledge levels were very high for modes of transmission and prevention of HIV/AIDS. Despite this knowledge, poor behavioural change among learners is a major setback thus increasing high risk of contracting HIV. Adequate knowledge about issues of cure, HIV testing and treatment was of concern in the findings in this study. Furthermore, data from qualitative interviews with the teachers highlighted the lack of multisectoral response to HIV/AIDS in Bergville rural communities which thus compromise the effectiveness in management of HIV/AIDS in schools. In summary, the study revealed some of the challenges faced by teachers and learners in regard to HIV/AIDS education. / South Africa

Magister Psychologiae - MPsych / Alcohol remains the most commonly abused substance in South Africa and several studies have shown associations between alcohol use and risky sexual behaviours, which pose a risk of HIV infection. Research indicates that the age group of 15-24 years is a high risk group for HIV infection. This study aimed at examining the perceptions of alcohol as a risk factor to HIV infection amoungst a sample of university students.Specifically, this study tested the hypotheses that most students perceive that those who consume alcohol were more likely to engage in unprotected sex, sex with multiple partners, casual sex and transactional sex. The Information Motivation Behavioural(IMB) skills model provided the theoretical framework for the study. Using a quantitative research design, a survey questionnaire was used to collect the data. The sample consisted of 240 first year psychology students (192 females, 48 males). Data analyses indicated support for the hypotheses that alcohol consumption was perceived as high risk for unprotected sex, casual sex and sex with multiple partners. However, the data showed no support for the hypothesis of alcohol increasing the risk of transactional sex. The data also indicated that non-drinkers were more likely to perceive alcohol as a risk factor than drinkers. The recognition by students of alcohol as a risk factor for HIV infection provides an opportunity for raising awareness about safer sex practices at institutions of higher learning in South Africa.

Philosophiae Doctor - PhD / All research involving human subjects should be conducted in accordance to the general ethical principles of autonomy or respect for persons, beneficence and justice. Competent adults can exercise their autonomy and can choose to take on risk for the sake of others, therefore are able to protect their own interests while in the pediatric research the ‗best interests of the child‘ takes precedence over autonomy. In other words giving informed consent in the pediatric context, is not ‗who decides‟ but „what is the best decision for the child‟. Due to lack of consensus gold standard to guide researchers and assess the quality of parental informed consent in Botswana, the practical and ethical challenges posed in obtaining parental informed consent for child enrolment in pediatric HIV clinical trials were examined. The study aimed to determine the readability of the consent forms used in pediatric HIV clinical trials; assess communication methods, practices and perceptions of the trial staff regarding the informed consent process; assess the extent to which parents recall and understand the information disclosed to them and their satisfaction with the informed consent process as well as to identify and describe the reasons for parental approval to child enrolment into HIV clinical trial studies.

HIV/Aids has become a household term in South Africa. Most people are aware of the existence of the disease and how it is transmitted. Several people have used this information as the impetus for behaviour change but there are many individuals who have not heeded this call and have not made any significant changes to their lifestyles. This is reflected in South Africa’s high infection rate. It would seem as if, for various reasons, people know how to protect themselves but have not used this knowledge to guard against possible infection. The purpose of this study is to explore the reasons why people have not changed their behaviour and to identify possible techniques that can be used to amend this situation. This will take the form of an intensive three-day prevention workshop where participants will be asked to think critically about their own behaviour. The aim of the programme will be to discuss, demystify and debate ideas. How will this programme be designed? The researcher will make use of focus groups consisting of Technikon students who will offer their thoughts and opinions. Once these focus groups have been conducted the researcher will undertake an intensive analysis of the data and identify certain key issues. A literature review will then follow. Therefore, the foundation of this programme will be based on the ideas of the participants, the researcher’s ideas and some points from formal behaviour change theories. The goal of this study is to add to the already growing body of HIV/Aids prevention literature and to design a programme that is useful and relevant. / Dissertation (MA (Counselling Psychology))--University of Pretoria, 2006. / Psychology / unrestricted

The incidence of HIV and AIDS is rising rapidly and has become a serious concern in South Africa. In order to address the HIV and AIDS problem, Community Based Care was introduced to render an effective service to the HIV and AIDS patient. The volunteers receive training to equip them to render a holistic service to the HIV and AIDS patient. The researcher’s concern is that despite the training programme offered, there are still problems regarding the service delivery by the volunteers. Volunteers focus on the physical needs of the HIV and AIDS patient only and do not attend to their psychosocial needs, despite the fact that they are trained to take care of the needs of the HIV and AIDS patient from a holistic approach. Due to this problem, the researcher decided to explore the experiences of the volunteers regarding the implementation of the training programme on HIV and AIDS Community Based Care in order to find answers as to why they do not attend to the psychosocial needs of the HIV and AIDS patient, although they were holistically trained. The research question was formulated as follows: What is the experience of volunteers in the Potchefstroom Municipality regarding the implementation of the training programme on HIV and AIDS Community Based Care? The researcher used a quantitative approach to explore the research question. Twenty (20) volunteers from the two Community Based Care programmes, namely Baptist Children’s Centre and Bambanani Youth Project, were randomly selected for inclusion in the study. The data collection method used was a group questionnaire. Three themes were explored, namely, the content of the training programme, presentation of the training programme and empowerment of the volunteers to render an effective service to the HIV and AIDS patient. The findings showed that volunteers experienced limitations regarding the content and the presentation of the training programme, and much so in the area of attending to the psychosocial needs of the HIV and AIDS patient. They recommended changes to the training programme, based on their experiences in practice. / Dissertation (MSW)--University of Pretoria, 2008. / Social Work and Criminology / unrestricted

The development of a safe and effective HIV vaccine remains challenging due to its high antigenic variability. Poxviruses are large, stable, and have a track record of use as human vaccine candidates. Recombinant fowlpox virus 9 (rFP9), a highly attenuated host range-restricted poxvirus strain, has been safely administered to humans with no ill effects, and is known to be immunogenic. This thesis describes the construction of complex rFP9 encoding various sequences of SIVmac239. The SIVmac239/macaque model is widely used for HIV vaccine development. The ultimate aim of this work was to combine the advantages of FP9 with those of live attenuated SIV to produce a safe yet hopefully effective model HIV vaccine candidate. Transfer plasmids for five different insertion sites within the FP9 genome were designed and constructed. Homologous recombination (HR) of adjacent FP9 sequences was employed to facilitate the integration of SIVmac239 sequences into the FP9 genome. Positive rFP9 were identified by blue colouration in presence of X-gal using a transient colour selection (TCS) technique, and the final markerless pure recombinants were confirmed by PCR. Expression of the target SIV proteins in the presence of T7 polymerase has been demonstrated by immunocytochemical (ICC) staining and Western blotting (WB) assays. Expression was also quantified by enzyme-linked immunosorbent assay (ELISA) in various cell lines at multiple time points. Five different unique rFP9 have been constructed through this project. All SIVmac239 open reading frames (ORFs) save nef have been integrated into the FP9 genome, and protein expression demonstrated where possible. Moreover, a single rFP9 vector expressing the defective SIVmac239 genome driven by T7 RNA polymerase has been successfully constructed and validated using a green fluorescent protein marker.rFP9 showed appropriate transgene expression in both avian and mammalian cells, although at different levels. The expression efficiency of rFP9 was finally compared to another attenuated poxvirus vector, modified vaccinia Ankara (MVA). Comparing the protein expression levels between rFP9 and rMVA was quite difficult because different poxvirus promoters (early/late in rFP9; intermediate in rMVA) were used to direct the transcription of the T7 RNA gene. Given this limitation, although generally higher levels of expression were seen with rFP9, this cannot be attributed to the FP9 with any certainty.

No description available.

HIV-1 is the causative agent for AIDS and has been a major focus of research for the past two decades. Though there is a combination therapy in place known as the “Highly Active Anti-Retroviral Therapy” (HAART), its usefulness is confounded by the generation of escape mutants, a host of side effects, and its prohibitive cost. The most useful alternative would be the prevention of infection by vaccination. Vaccine research has been focused on the use of recombinant protein sub-units of the virus or combinations thereof to elicit a neutralizing response against the virus. These approaches have mostly resulted in a failure to generate broadly cross reactive neutralizing response against primary strains of the virus. The work reported herein is aimed at designing a rigidified version of gp120/gp120 derivatives and understanding the scope of the various antigenic regions in gp120 in generating a neutralization response. Chapter one discusses some general features of the virus and the immune system. The general nature of AIDS, its spread and its immunological characteristics are also described in this chapter. Chapter two discusses the design and NMR structural analysis of gp120 bridging sheet peptide mimics in methanol and water. The structure of gp120 can be loosely divided into two domains (the outer domain and the inner domain) that are linked together by a discontinuous four stranded antiparallel beta sheet known as the bridging sheet. The bridging sheet is known to overlap with the coreceptor binding site of gp120 and hence is a suitable target for designing virus-entry inhibitors. 17b, a neutralizing antibody isolated from an infected individual, is known to bind to this region of gp120. Our aim in this part of the work was to design a four stranded antiparallel beta sheet, based on the sequence of the bridging sheet, that would contain most of the residues involved in 17b binding. NMR and CD studies confirmed that the peptide was well structured in methanol but the structure was largely lost on addition of aqueous solvent. A small population of the peptide was found to be well-folded in aqueous solution. Chapter three discusses the design and characterization of a gp120-CD4D12 single chain. It is well known that the conformation of gp120 changes upon binding CD4 to expose cryptic epitopes, known as CD4i epitopes. In this work we report the generation of a single chain gp120-CD4 construct that has the cryptic epitopes exposed. The construct bound to 17b, a conformation specific antibody against the bridging sheet of gp120, a cryptic epitope, as well as a non-covalent complex of gp120:CD4D12. There was also very insignificant secondary structural change in gp120 upon complex formation with CD4D12 as observed by CD spectroscopy. Immunological studies with DNA and protein vaccination in guinea-pigs indicated that though 17b like antibodies are generated after immunization, they did not contribute towards the neutralization of primary isolates of the virus. It was also observed that it was the anti-CD4D12 antibodies that were responsible for the neutralization by the sera. These studies indicated towards the inability of the bridging sheet to generate effective neutralization response in case of vaccination with gp120/CD4 complexes. Chapter four discusses the design of a mimic of the gp120/CD4 complex. Since it was seen from our previous work that gp120/CD4 complexes generate a large fraction of antiCD4 antibodies and hence are unsuitable for vaccination purposes, we generated a construct with the minimal binding region of CD4. The small fragment of CD4 spanning from 21st residue to 64th residue was inserted in the V1/V2 loop of gp120. The insertion site was designed based on the region of gp120 closest to this fragment and capable of tolerating insertions. This protein did not bind to 17b as well as gp120/CD4 complex but showed a higher binding compared to full length gp120. Further immunological characterization with this protein revealed that it was not capable of generating neutralizing antibodies against the virus. Chapter five discusses the design and execution of a SPR based solution phase competition experiment to find the solution phase binding constant of CD4 and CD4 analogs to gp120. A major problem during the analysis of binding data obtained by SPR is the accurate determination of Rmax, a parameter needed to obtain an accurate equilibrium dissociation constant. In this chapter we have developed a binary as well as a ternary solution phase SPR based assay to accurately determine a solution phase equilibrium binding constant. The binding constants were determined for gp120 binding to CD4D12 and other CD4 analogs. To confirm the validity of the assay, a control antigen:antibody interaction whose equilibrium dissociation constant has been determined by other methods has been used as a test case. Chapter six discusses the design and characterization of V3 peptides inserted in the loop regions of E. coli Thioredoxin (Trx). Trx has earlier been used to display random peptide libraries between the 33rd and the 34th residue. We have constructed three constructs where the peptide has been inserted between the 33rd and 34th residue, between the 74th and 75th residue and between the 84th and 85th residue. The insertion between 74th and 75th position (74V3Trx) was found to be superior to the other two and would be a suitable alternative for display of a random peptide library. The binding of these constructs to 447-52D, a V3 peptide specific antibody was characterized. These were also characterized immunologically, and 74V3Trx was found to generate weakly neutralizing activity against the MN strain of HIV-1. Competition experiments with 447-52D with these sera indicated that there were antibodies generated that could compete out 447-52D binding to gp120 but not in sufficient concentration to provide broad neutralization. Appendix 1 discusses the rational design of disulfides to stabilize proteins based on the analysis of naturally occurring disulfides. In our attempts to design a rigidified version of gp120 we had designed disulfides in gp120 based on its crystal structure. Many of these were disulfides that would span antiparallel adjacent strands. In order to improve the design principles, we analyzed naturally occurring disulfides that span antiparallel adjacent strands and characterized them in terms of their positional preference in a beta sheet. It was found that these disulfides mostly occur on edge strands and are found exclusively between non-hydrogen bonded registered pairs of adjacent antiparallel strands. Mutagenesis on Thioredoxin was performed to verify our results. It was found that disulfides designed between the non-hydrogen bonded pairs of antiparallel strands could significantly stabilize the protein whereas the ones between hydrogen bonded pairs destabilized the protein.

This research focuses on the psychosocial factors that affect adherence to highly active antiretroviral therapy (HAART) amongst HIV/AIDS patients at Kalafong Hospital. Even though the development of such regimens has helped turn HIV infection in the United States into a relatively manageable, though still serious chronic disease, compliance remains one of the major challenges in managing medication for those patients living with HIV/AIDS. This is particularly relevant given the high adherence rate (95%) required to obtain a successful long-lasting effect. In South Africa non-compliance to HAART is an under-explored phenomenon. Consequently, an understanding of factors influencing compliance is still incomplete. A qualitative study that investigates non-adherence to medication in HIV/AIDS patients was undertaken at Kalafong Hospital. This study aimed to understand patients’ psychosocial difficulties resulting in non-adherence. The study was approached in terms of the health belief model (HBM), which addresses individual characteristics pertaining to change, the transtheoretical change model (TTM) and the motivational interviewing model (MI), which address both individual and social contexts pertaining to change. The findings are designed for use by healthcare professionals as a proactive compliance enhancement tool. Participants were recruited through referrals by the medical staff to the researcher. The criteria included that participants had relapsed due to non-compliance with drug therapy. Participants that were currently experiencing difficulties with adherence were also included in the study. Males and females aged between 20 and 40 were included in the study. Fifteen participants between the ages of 20 and 40 participated in the study (13 females and two males). The data were collected by means of semi-structured interviews and follow-up unstructured questions. The interviews were audio recorded and field notes were taken. Data were analysed qualitatively. Sixteen themes emerged and were further classified into two categories: individual and social context. The themes were then compared and integrated with the literature. The study concludes that psychosocial factors such as support from family, friends and healthcare workers was found to be of utmost importance in encouraging adherence. Medication can only prolong a patient’s life if the psychosocial context in which the patient is embedded is considered in the treatment plan. / Dissertation (MA)--University of Pretoria, 2008. / Psychology / unrestricted