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This research has focused on the development of novel coumann derivatives containing peptide-like side chains as potential HIV-1 protease inhibitors. The reaction of various salicylaldehyde derivatives with tert-butyl acrylate In the presence of 1,4- diazabicyclo[2.2.2]octane (DABCO) has afforded a series of Baylis-Hillman adducts in moderate yield. Cyclisation of the adducts in the presence of HCI afforded the corresponding 3-(chloromethyl)coumarin derivatives, which have been reacted with various amine hydrochlorides in the presence of Proton Sponge® to afford a series of novel 3- (aminomethyl)coumarin derivatives, which were fully characterised by NMR and HRMS methods. Various approaches to the introduction of hydroxyl or amino groups at the C-4 position of coumarin and the 3-(chloromethyl)coumarin derivatives have been explored; these have included dihydroxylation of the coumarin double bond, and the synthesis of 4- benzylaminocoumarin derivatives as potential intermediates. The Vilsmeier-Haack and Mannich reactions have also been investigated as possible methods of introducing the desired peptide-like functionality. Computer modelling of selected structures has indicated that some of the novel 3- (aminomethyl)coumarin derivatives may exhibit activity as inhibitors of HIV-1 protease. The planned enzyme inhibition assays were unfortunately precluded by the aqueous insolubility of the selected compounds. Three ¹³C NMR chemical shift algorithms, viz., Modgraph Neural Network, Modgraph HOSE and Chern Window, have been applied to selected compounds prepared in this study. The Modgraph Neural Network algorithm was found, in all cases, to provide the most accurate correlations with the experimentally-determined chemical shifts. / KMBT_363 / Adobe Acrobat 9.54 Paper Capture Plug-in

Meningitis remains a frightening disease with a high morbidity and mortality in spite of optimal treatment. In South Africa in particular, the incidence of HIV-infected patents with meningitis has risen considerably during the past decade. The first part of this meningitis study evaluated prognostic indicators in meningitis. In 100 adult patients with meningitis it was found that the Glasgow Coma Scale (GCS) at admission was a good indicator of the ultimate prognosis of the patient, with a GCS value of > 12 associated with a good outcome in 88% of patients. A GCS value of < 8 predicted an unfortunate outcome in 88% of patients. A high CSF protein level was also associated with an unfortunate outcome but the statistical significance was not as marked as with the GCS value. Age, CSF-neutrophil count, and glucose levels were also evaluated as possible prognostic indicators but were not found to be statistically significant. The electroencephalograms of 12 patients with pneumococcal meningitis showed that a grade 4 dysfunction within 48 hours of admission indicated a poor outcome; CT brain scans of 26 patients with TB meningitis showed that an adverse outcome was seen particularly in patients with TB meningitis and infarcts while in 33 patients with bacterial meningitis no specific sign was found to indicate a bad prognosis - probably due to the small number of patients evaluated. Prognostic factors in cryptococcal meningitis were lastly evaluated retrospectively in 44 patients; age, CSF white cell count and CD 4 counts were not found to be associated with outcome, while a GCS value of ≤ 14 at admission was found in almost three quarters of patients with an eventual adverse outcome. The second part of the study evaluated the impact of HIV-infection on meningitis. Between 1994 and 1998, the HIV-epidemic caused a marked shift in the spectrum of meningitis towards chronic infections such as TB and cryptococcal meningitis, while the incidence of HIV-related cases with meningitis rose from 14% in 1994 to 5% in 1998. A comparison of clinical, CSF and pathological findings and outcomes in 20 HIV-positive and 17 HIV-negative patients with tuberculous meningitis showed that HIV-infection does not significantly alter clinical and CSF findings in TB meningitis in South Africa, but ventricular dilatation and infarcts occur more frequently in HIV-positive patients. Diagnostic aids in meningitis were assessed in the final part of this study. The polymerase chain reaction for TB was measured in the CSF of 10 patients with suspected tuberculous meningitis and disappointingly only positive in two patients in spite of positive CSF cultures for TB in an additional four patients. Lymphnode biopsies were performed on seven patients with intracranial tuberculosis. Excision biopsy of an enlarged Iymphnode showing caseating granulomas and/or acid-fast bacilli confirmed the diagnosis of TB within 48 hours of admission. Thus, Iymphnode biopsies may be an effective and practical aid in diagnosing intracranial TB. Adenosine deaminase (ADA) levels are often elevated in both tuberculous and bacterial meningitis. ADA iso-enzymes analysis in 26 patients however, showed that the ADA2 iso-enzyme was the major contributor to increased ADA activity in the CSF of patients with tuberculous meningitis and not with bacterial meningitis. The EEG was evaluated as diagnostic aid in 55 patients with meningitis to discriminate between viral and non-viral meningitis. Sensitivities of 70% and 80% of VEEG and QEEG's respectively were attained for the prediction of patients with non-viral meningitis, while the VEEG had a specificity of 100% for the prediction of viral meningitis. / Thesis (MD (Neurology))--University of Pretoria, 2005. / Neurology / unrestricted

This study focuses on Indian secondary school youths’ understanding of sexual violence in their community in the age of HIV and AIDS, and the contribution that participatory video can make to address sexual violence. South Africa, apart from having the highest HIV prevalence in the world, also has the highest incidence of sexual violence. South African society often appears complacent about the high levels of sexual violence. In the Indian community, especially among the youth, sexual violence is also cause for concern. Much effort and energy has been expended in educating learners about sexual violence and HIV and AIDS with the objective of raising awareness of the dangers of engaging in risky sexual behaviour, and ultimately to empower and influence positive behaviour change. Because HIV prevalence in the Indian population is on the rise, Indian youth’s particular vulnerability is the reason for focusing on how they understand sexual violence in the age of AIDS. Besides the paucity of research on Indian youth and sexual violence, the methodologies which have been used produced research which is descriptive in nature and hence a methodological shift from traditional methodologies to a participatory visual methodology which has the potential for critically engaging the Indian youth on the issues of sexual violence, could contribute to research which has a social change focus. This qualitative research therefore uses a visual participatory methodology within a critical research paradigm, to explore and contribute to addressing the problem of sexual violence in the age of HIV and AIDS. The participants in the study, a sample of 20 Indian learners (10 boys and 10 girls), from a secondary school in Durban which has predominantly Indian learners, was purposively selected from Grade 11 classes. Participatory video enabled them to voice how they understand sexual violence and in doing so move towards reflecting on their own agency. The theory of triadic influence with its three streams, i.e. cultural attitudinal, social normative and intrapersonal, was used to make meaning of the findings. It also provided a frame for a fourth path, namely the preventive intervene. While participatory video enabled exploring Indian youths’ understanding of sexual violence in their community in the age of AIDS, it at the same time enabled them to reflect on, and perhaps begin to disrupt their understanding of the cultural attitudinal, social normative and the intrapersonal influences and how these influence their thinking about sexual violence. Two a priori themes were established prior to the analysis, to respond to how Indian youths understand sexual violence in the age of AIDS, and how participatory video can address sexual violence. The findings suggest that their understanding of sexual violence stems from a culture of concealment in which veiling sexual violence is the norm; that the vulnerability of youth increases as the experience of pressure from peers to engage in sexual violence increases; and that sexual violence is traumatising. The use of participatory video increased the youths’ reflexivity and created a space for them to explore how to take action. The findings imply that addressing sexual violence with Indian youth should begin with interrogating the cultural norms of masculinities and femininities, and the cultural practices rooted in traditional structures of the family and community which perpetuate gender disparities and the restriction of the autonomy of women and girls. Addressing issues of vulnerability and sexual violence should be the focus of all school and community interventions to ensure learners’ well-being and ability to resist negative peer pressure. These interventions should encourage self-reflection and raise social awareness through active participation and in so doing bring about social change in the Indian community. Vigorous participatory interventions which draw on the voices of the Indian youth as agents of social change in addressing sexual violence in the age of HIV and AIDS, is therefore urgent. The significance of this study as research as intervention is useful in enabling the exploration - with the Indian youth - of how cultural and religious norms, gender disparity, Indian masculinities and femininities, and social peer pressure feed into youth’s understanding of sexual violence and at the same time getting them to begin rethinking, challenging and disrupting these understandings where necessary. The study demonstrates that engaging youth affords them an opportunity to draw from their own experiences and through their own voices and actions create knowledge through participatory video, thereby making a contribution to visual methodologies and research around sexual violence and HIV and AIDS in their world.

Mindfulness research is growing considerably, though there is very little research in the area of HIV and mindfulness. This study explored and described the experience of a sample of HIV positive people, before and after an 8 week Mindfulness Based Stress Reduction (MBSR) programme, to ascertain whether mindfulness can positively impact the CD4 count of the participants, with the consequent improvement to their immune systems. The incidence of depression, anxiety and stress levels were also explored. The research sample consisted of 17 participants recruited from a local hospital clinic. Purposive sampling was used to source participants. The mixed method approach of data gathering was made up of a pre-test post-test battery of questionnaires and blood tests. Mindfulness levels were assessed with the Five Facet Mindfulness Questionnaire (FFMQ) and Mindfulness Attention Awareness Scale (MAAS) at 3 intervals, while depression, anxiety and stress were assessed by means of the Depression Anxiety Stress Scale (DASS-21). Key findings included the following: the drop out rate for this population group was large, mindfulness practices do not always have a positive effect on immune functioning when there are other confounding variables at play, all participants reported they benefited from the 8 week MBSR course, though their results did not always indicate this. In conclusion it is proposed that mindfulness is potentially beneficial.

The standard anti-retroviral drugs (ARVs) used for the treatment of HIV/AIDS have significant side effects resulting in a lack of adherence and the emergence of multidrug resistant viral strains. These drugs are also expensive, making it essential to investigate all alternatives to classical HIV/AIDS treatment. A wide variety of nonconventional medicines are used by patients for the treatment HIV and for symptoms associated with HIV. So long as they are safe and effective, traditional, complementary and alternative medicines (TCAMs) may be considered more advantageous for developing countries as they are relatively cheap, more accessible and widely accepted by local populations. The aim of this study was to determine the prevalence of TCAM use in HIV-positive patients, prior to, and during ARV therapy. The study was exploratory, cross sectional and observational in nature. Participants were selected via convenience sampling from the Nelson Mandela Bay Municipality, and included 244 HIV-positive patients, 29 health care professionals (HCPs) and 30 traditional, complementary and alternative practitioners (TCAMPs). A wide variety of TCAMs were used by the sample population. These medicines were more commonly used by non-ARV patients (36 percent) compared with ARV patients (22 percent). A significant statistical difference in TCAM use between the ARV and non- ARV population was found in relation to education, employment, period of status awareness, patient opinion of personal health and the reasons for TCAM use. Amongst the HCPs, 24 percent recommended TCAM use prior to ARVs, and 55 percent were aware of patients self-prescribing before and during ARV treatment. Amongst the TCAMPs, 90 percent provided a wide range of TCAMs for HIV, with some giving consideration to conventional management. TCAMs are commonly used by HIV-positive patients on ARVs, as well as by those not on ARVs. These medicines are also the preferred form of treatment for those not seeking conventional treatment. TCAMs are widely available and recommended by TCAMPs as well as some HCPs. Due to public health concerns, clinical trials of the widely used TCAMs are crucial in order to establish the safety and efficacy of these medicines in HIV.

This thesis explores the psychosocial dynamics of sexual risk-taking in men who have sex with men, with particular focus on the dilemmas that gay men face in establishing trust in themselves and reasonable trust and intimacy with their sexual partners. As well, the practical function of this study is to analyze past and current social marketing efforts aimed at reducing the spread of HIV/AIDS, and to offer suggestions for how to approach a strategy to reduce HIV incidence in gay men and at the same time bolster efforts to assist men who have sex with men (MSM) in adhering to safer sex guidelines. In part, this thesis uses a sample of participants of the Vanguard Project cohort (St. Paul's Hospital, Vancouver, British Columbia), in order to explore the social meanings attributed by MSM towards sex, risk, intimacy, and attitudes toward HIV/AIDS. Through the use of first-person narratives, this thesis examines the concordance or discordance of MSM beliefs and behaviour with long-standing theoretical models of harm reduction methods concerning sexual risk. The study reveals that, in great measure, due to past life course events, many gay men suffer from a lack of trust in themselves, which results in a tendency to make irrational or unreasonable decisions concerning their long-term sexual health, and a lack of trust in other gay men. As welL through the misguided and often untruthful health models that advocate fewer sexual partners and rely upon the false assumption that all potential sex partners are carriers of contagion, the sense of mistrust has been reinforced. The lack of confidence in self and others further translates into a suspicion of the motives and/or efficacy of social institutions entrusted with community health development and maintenance, rendering their efforts even less effective. Moreover, traditional harm reduction messages, especially 'fear campaigns', often act as a deterrent, rather than as an incentive, to harm reduction. Of more appeal are supportive harm reduction messages delivered by someone whom the recipient trusts, especially when the social meanings of sex, risk, trust and intimacy are, for many gay men, less fixed and more contingent than for the population at large. This means that attempts to modify risky behaviour must acknowledge and negotiate multiple meanings, shifting values and changing social climates, as well as routine epidemiological concerns. The research identifies four key themes within a problematic of trust, risk and intimacy, and delineates the harm reduction social complexities experienced by gay men in the study group; these recurring themes deal with family and early sociahzation, internalized homophobia, contingency and instability of meanings of risk, trust and sex, and the toistworthiness of the messengers of harm reduction strategies. Out of these recurring themes come a number of recommendations for remedial programs aimed at both mid- and long-term reductions in HIV incidence. The recommendations are grounded in the recognition that homophobic and/or dysfunctional social conditions are, to a great extent, implicated in sexual risk behaviour, and therefore must be eliminated or ameliorated before meaningful harm reduction gains can be realized. The discussions with the gay men in the study reveal their need for positive role models and communal social support in their efforts to combat HIV infection, suggesting a need to rethink the meanings of what it is to be gay, a need to redevelop and revitalize what was once a vibrant and cohesive corrimunity, and bearing in mind the lessons of the past, a need to re-approach the task of sternming the tide of HIV infection in ways that are sensitive to the factors that adduce high-risk sexual behaviour. / Arts, Faculty of / Sociology, Department of / Graduate

M. Tech. / Since year zero of the HIV/AIDS pandemic, homosexuality has been linked to HIV/AIDS (Hooper; 2000). HIV positive homosexual individuals, therefore, are exposed to double stigmatisation; that of being homosexual and of being infected with HIV/AIDS. Taking into account the link between psyche, neural and immunological function, the above statement directly impacts the pathophysiology and prognosis of HIV/AIDS (Forrest and Kanbus; 2004) (De Kooker; 2002). This study examines the psychological and emotional states of the subjects, which are influenced, not only by their disease state but also by social stigmatisation. The aim of the study is to obtain a comprehensive homoeopathic symptom picture of HIV positive homosexual males within a South African context, compare this to existing homoeopathic symptom pictures, discuss HIV/AIDS in terms of miasmatic theory and consider possible homoeopathic treatment options for HIV/AIDS. This is a qualitative pilot study. Fourteen HIV positive homosexual males, of varying race, were recruited through Caritas Care and interviewed in Gauteng. The participants were between the ages of twenty and fifty and in stage one to three of HIV infection. Six of the participants were on antiretroviral therapy, eight not. The participants were interviewed using set questionnaires and underwent a physical examination. The interview transcripts were analysed and compared to each other then commonalities extracted to obtain a composite symptom picture. The composite symptom picture was compared to existing genus epidemicus symptom pictures and existing nosode proving pictures. The composite symptom picture was analysed using Cara Pro computerized repertorisation to determine possible treatment options. This computer programme affords the user access to multiple repertories simultaneously for rubric selection, and then analyses the case allowing for the use of different strategies. The composite symptom picture was also analysed in terms of miasmatic characteristics. The study concludes that the composite symptom picture partially matches existing HIV/AIDS genus epidemicus symptom pictures and nosode proving pictures. The composite symptom picture exhibits prominent themes of mental and emotional restlessness, generalized weakness, rebelliousness, desire for control and a desire for warmth. Possible treatment options are indicated. The include the remedies Sepia, Apis mellifica, Bryonia alba, Iodium and Natrum carbonicum but particularly of the Flouratum mineral group remedies such as Calcarea fluorica and Acidum flouricum. The study indicates that HIV/AIDS is emerging as a new miasm exhibiting characteristics of the Sycotic and Tuberculinic miasms. / Dr. L. Solomon Dr. T. Blake

MPH / Department of Public Health / South African HIV epidemic remains the largest in the world with an estimated 7.7 million people living with HIV in 2018. It accounts for a third of all new HIV infections in southern Africa. In 2018, there were 240,000 new HIV infections and about 71,000 South Africans died from AIDS-related illnesses. To meet the 90 90 90 targets by the end of 2020, patients are subject to uncompromising and long-term commitments of taking at least 95% of their treatment as prescribed. Evidence shows that patients are not adhering to treatment regardless of the systems that the government has initiated. The purpose of this study was to identify factors contributing to non-adherence levels to antiretroviral therapy amongst adults living with HIV and AIDS in Makhado Municipality. A quantitative, descriptive approach was adopted. Data was collected using a questionnaire with closed ended questions. The targeted population was made up of males and females between the ages of 18 to 59. Validity and reliability were ensured in the study. Pretesting was done in Kulani Gateway clinic and 10 respondents were selected. A sample of 225 respondents was selected from the targeted population using convenience sampling. Data analysis was done using statistical package for social sciences (SPSS) version 25.0.The analysed data were presented in tables/percentages and charts. The findings revealed that most respondents(80%) who have been on treatment for less than six months adhere more to treatment than respondents who have been on treatment for more than 24 months (57%). The studies also revealed that about 57.9% of respondents forget to take treatment when they have taken alcohol and 42.1% took their treatment even when they have taken alcohol. Side effects were identified as barriers to adherence. The study indicated most respondents (73.3%) experienced side effects especially in the first few months of commencing treatment. and about 26.7% did not report any side effects. In conclusion, Non-adherence to ART poses a major challenge in most regions of the world and in all stages of HIV infection. When patients adhere to treatment the virus will suppress, quality of life will improve and patients will also prevent cross infections. The study revealed factors contributing to nonadherence to ART that includes alcohol intake and side effects. The study also indicates a strong association between waiting times as a factor to improve on adherence. Therefore the study recommends that an intervention to address alcohol intake and side effects should be carried in Makhado Local Municipality. / NRF

This research presents a proposal for the assessment of technology to manage antiretroviral treatment. The system called Cell-Life has been successfully tested at a pilot site in Gugulethu, Cape Town from September 2002 till date and offers a cost-effective solution for adherence monitoring, side effect management, effective home based care and reducing pill count dependence at the clinic. With the aid of the Cell-Life SIM card menu (please see Appendix A, page 63) on a cell-phone the therapeutic counsellor is equipped with a live-link to the clinic or doctor while visiting patients. The menu allows entering data about the patient's drug adherence, side effects and symptoms, scheduling visits to the clinic and alert messages. The data is sent using short message service (SMS) and stored in a database, which can be accessed via the Internet by a doctor who will receive a complete report on the patient's status quo. The main benefits of the system lie in creating a communication link between the clinic/doctor and the therapeutic counsellor at minimal cost. Another benefit is the collection of reliable data relating to drug adherence and the minimising of human error through preset menu options on the phone. The pilot study has shown that management of anti-retroviral therapy is possible in resource-constraint urban settings. But for a provincial or national rollout of the Cell-Life system, the challenge is the lack of the required infrastructure, technology, personnel and logistics for effective operation of the Cell-Life systems specifically in the rural areas of South Africa. This research investigated the availability of the Cell-Life requirements in the Western Cape. The findings showed that the Cell-Life systems could be implemented in the health regions investigated across the Western Cape. It was also shown that an in depth needs assessment study is required before implementing the Cell-Life system in any community.