Magister Pharmaceuticae - MPharm / Many studies have reported low cure rates for multidrug-resistant tuberculosis (MDRTB) patients and MDR-TB patients co-infected with human immunodeficiency virus (HIV). However, little is known about the effect of HIV infection and antiretroviral therapy on the treatment outcomes of MDR-TB in South Africa. Therefore, the objectives of the study are: to find out whether HIV infection and interactions between ARVs and second line anti-TB drugs have an impact on the following MDR-TB treatment outcomes: cure rate and treatment failure at Brewelskloof Hospital. MDR-TB patients were treated for 18-24 months. The study was designed as a case-control retrospective study comparing MDR-TB treatment outcomes between HIV positive (cases) and HIV negative patients (controls). Patients were included in the study only if they complied with the following criteria: sensitivity to second line anti-TB drugs, MDR-TB infection, co-infection with HIV (for some of them), male and female patients, completion of treatment between 1 January 2006 and 31 December 2008. Any patients that presented with extreme drug-resistant tuberculosis (XDR-TB) were excluded from the study. Data were retrospectively collected from each patient’s medical records. There were a total of 336 patients of which 242 (72%) were MDR-TB patients and 94 (27.9%) MDRTB co-infected with HIV patients. Out of the 242 MDR-TB patients, 167 (69.2%) were males and 75 (30.7%) were females. Of the 94 patients with MDR-TB co-infected with HIV, 51 (54.2%) males and 43 (45.7%) females. Patients with multidrug-resistant tuberculosis co-infected with HIV who qualify for antiretroviral therapy were treated with stavudine, lamivudine and efavirenz while all MDR-TB patients were given kanamycin, ethionamide, ofloxacin, cycloserine and pyrazinamide. The cure rate of MDR-TB in HIV (+) patients and in HIV (-) patients is 34.5% and 30 % respectively. There is no significant difference between both artes (pvalue = 0.80). The MDR-TB cure rate in HIV (+) patients taking antiretroviral drugs and in HIV (+) patients without antiretroviral therapy is 35% and 33% respectively. The difference between both rates is not statistically significant. The study shows that 65 (28.0%) patients completed MDR-TB treatment but could not be classified as cured or failure, 29 (12.5%) patients failed, 76 (32.7%) defaulted, 18 (7.7%) were transferred out and 44 (18.9%) died. As far as treatment completed and defaulted is concerned, there is no significant statistical difference between HIV (+) and HIV (-) The number of patients who failed the MDR-TB treatment and who were transferred out is significantly higher in the HIV (-) group than in the HIV (+) group. Finally the number of MDR-TB patients who died is significantly higher in the HIV (+) group). The median (range) duration of antiretroviral therapy before starting anti-tuberculosis drugs is 10.5 (1-60) months. According to this study results, the MDR-TB treatment cure rate at Brewelkloof hospital is similar to the cure rate at the national level. The study also hows that HIV infection and antiretroviral drugs do not influence any influence on MDR-TB treatment outcomes. / South Africa

Masters of Science / The rapidly expanding field of nanotechnology has been the focus of many biologists with regard to drug delivery. The ability of nanoparticles to enter cellular compartments makes it possible to explore specific treatment strategies for life-threatening diseases such as AIDS. Since HIV primarily infects CD4+ cells, we aim to use CD4 as a selectable marker to deliver pro-apoptotic nano-devices to HIV infected cells. The objective is to selectively induce cell death or apoptosis in CD4+ HIV infected cells. Apoptosis is activated through a number of biochemical pathways. The apoptosis promoting protease, caspase-3 is central to the induction of apoptosis. Caspase-3 is produced as an inactive zymogen and is activated by other proteases through proteolytic cleavage. We take advantage of the fact that HIV-infected cells produce HIV-1 protease, which is responsible for the production of infectious virions through proteolytic cleavage of the HIV proteins, Gag and Pol. Our strategy was to generate a mutant form of the caspase-3 protease that is only cleavable by HIV-1 protease.

Magister Public Health - MPH / In recognition of high dual burden of tuberculosis (TB) and Human Immunodeficiency virus(HIV) in Sub-Saharan Africa, the World Health Organization (WHO, 2004) provided guidance for implementing integrated HIV/TB services. This strategy has been implemented using different models ranging from partial to fully integrating, and evaluations of these models have been conducted to determine their effectiveness. The aim of this study was to describe and contrast the effectiveness of different models of implementation of HIV and TB integration at primary care level within the Tuberculosis (TB) programme in Livingstone District, Zambia The specific objectives of the study included; 1. To describe the models of integrated HIV and TB services that are currently implemented at four health facilities within the TB programme in Livingstone District at primary health care level. 2. To describe and contrast the coverage and quality of HIV diagnosis in the Tuberculosis(TB) programme achieved in the different facilities representing fully and partially integrated models of service delivery. 3. To describe and contrast the coverage and quality of HIV prevention activities in the Tuberculosis (TB) programme achieved in the different health facilities representing fully and partially integrated models of service delivery. 4. To describe and contrast the coverage and quality of HIV care activities received by coinfected clients in the Tuberculosis (TB) programme in the different facilities representing fully and partially integrated models of service delivery. 5. To describe the quality and outcomes of TB diagnosis and treatment in the different facilities representing fully and partially integrated models of service delivery. A research design using quantitative methodologies: a cross sectional survey and structured observations or review of patient records (quantitative) were used. The records of 814 TB clients notified in 2010 served as the study population while the sample of 464 (232 from partially and 232 from fully integrated) were randomly selected. Two data collection tools namely: patient record and HIV/TB register review; facility staff interviews (key informant interviews) were used and the results were analyzed using Epi info statistical package. In the study, all respondents gave informed consent and no personal information was collected from the retrospective record review. The HIV prevention interventions in this study were rated below 30% except for of HIV education (97%). Statistically significant differences (p-value<0.001) existed for condom provision at facility level. Poor performance reported for STI screening (below 2%) and PMTCT information (below 15%). The HIV testing rate was 94% among TB clients which was higher than the counseling coverage of 88%. Statistically significant differences (p value <0.001) at facility level existed for clients who received HIV test results. Sixty three percent (63%) of TB clients were also co- infected with HIV. ART assessment for TB clients was below 40% and statistically significant differences (p value=<0.001) between facilities were identified for this indicator. ART assessment of TB clients at the same facility they tested for HIV was above 50% for all facilities. The continuation of cotrimoxazole was poor at 38% and statistically significant differences (p value=<0.001) were identified for this indicator between facilities. Sputum testing was 85% while the cure rate was poor at 28% average for all facilities. Statistically significant differences (p-<0.001) were noticed at model level for clients cured. Although HIV prevention and care services were introduced in the TB program in Livingstone,they were not comprehensive enough to respond to the high HIV and TB co-infectivity. For HIV prevention, other than HCT and HIV education, the rest of the critical interventions such as condom provision, STI screening and treatment, and PMTCT intervention were neglected. The HIV care services such as ART assessment and CPT implementation were also poor. There is need to put in place systems to improve these services in the district to improve treatment outcomes. The differences that were noted in performance for the majority of the indicators were mainly at facility level as being a fully integrated facility did not guarantee effective integration or better performance.

The purpose of this study was to evaluate the impact of a HIV/AIDS module, taught for approximately 24 hours over eight weeks in six schools, on the knowledge, behaviour and attitudes of grade 11 biology learners, and to identify problems their teachers had in teaching the module. The module contains detailed scientific content on HIV/AIDS and outcomes-based assessment activities. The answers written by each learner in a pre-, post- and retention test and questionnaire that included both open and closed questions on general and functional knowledge, attitudes and skills were analysed for significant changes. A narrative written by each learner was analysed to determine how the module had dealt with issues that affected his I her life. A structured interview was conducted with each teacher to identify difficulties he I she experienced in implementing the module. Classroom observations were used to monitor the implementation of the intervention in order to provide information to verify the findings of the tests, questionnaires, narratives and interviews. Analysis of the tests and questionnaires showed a significant improvement in the means scored in the pre, post- and retention tests. An ANOVA showed that the difference was unlikely to be attributable to chance. Narrative analysis resulted in a number of common themes being identified. The learners were profoundly glad to have been taught this information and many of them provided evidence of how the module impacted on their lives and sexual behaviour. Their knowledge has empowered and motivated them to control their own lives. The teacher interviews established some of the common difficulties that the teachers experienced in teaching the module. These were verified by the classroom observations. The main problems were the lack of facilities and limited time to teach about HIV/AIDS. / Dissertation (MEd (Curriculum and Instructional Design and Development))--University of Pretoria, 2006. / Curriculum Studies / unrestricted

Aim To determine the demographic and socio-economic characteristics of patients accessing antiretroviral treatment, in the public sector in Zambia. Methods A descriptive cross-sectional survey, using a pre-structured interview questionnaire, with patients on antiretroviral treatment. A total of 200 patients receiving antiretroviral treatment at the 2 national referral hospitals and seven provincial hospitals providing ART were included in the study Data was analyzed using STATA version 8. Analysis was by frequency tables and summary statistics. Results The majority of the patients on antiretroviral treatment were females at 61.5 percent. Most of the patients were in the age group 40 - 44 years old. Most of the patients were married followed by those who were widowed, who were predominantly female. The net monthly income was generally low for most patients and the forty thousand Kwacha monthly contributions for ARVs was high for most patients. Higher levels of education were associated with increased access to antiretroviral treatment. Conclusion and Recommendations There were more females than males accessing antiretroviral treatment in the public sector in Zambia. The majority of patients have a low income and the forty thousand Kwacha monthly contributions towards ARVs was high for most patients. It is recommended that antiretroviral treatment be provided for free or at a highly subsidized cost and also that the Ministry of Health increases the ART centers if the goal to put 100,000 on treatment by the end of 2005 is to be achieved. / Dissertation (MPH)--University of Pretoria, 2009. / School of Health Systems and Public Health (SHSPH) / Unrestricted

AIDS is a leading high-risk disease with multiple-faceted impact worldwide. It is impacting on a number of sectors. This subject was chosen because of personal interest, and also because of lack of research on the subject in the South African Post Office (SAPO). The researcher’s work in Durban, at the SAPO as an Employee Assistance Professional for two years, has exposed her to an increasing number of employees infected and affected by HIV/AIDS. As an Employee Assistance Professional the researcher is expected to support these employees. Through working with employees who are infected and affected by HIV/AIDS the researcher felt interested in the subject, especially in investigating how HIV/AIDS is affecting SAPO. The researcher also wanted to contribute to increasing the knowledge base, and to contribute to the development of the organization. This study will assist management to gain insight into the impact of HIV/AIDS on the workplace, and then to be able to plan for the future. This study was focused on the impact of HIV/AIDS in the SAPO in Durban. It was designed to understand the psychosocial impact of HIV/AIDS on both the infected and the affected employees. The aim of the study was to explore the impact at in individual level and at the organization as a whole. A particular area of interest was on the impact caused by HIV/AIDS on their benefits and the execution of work of the employees. Data was gathered by a questionnaire through a sample of 33 supervisors and 10 managers from the Post Offices around Durban who were selected using systematic random sampling. Efforts were made to ensure that cultural diversity in the Post Office is represented in the sample. A literature review was conducted on the subject of HIV/AIDS and its impact in the workplace. Key concepts of the study were the following; Human Immunodeficiency Virus (HIV), Acquired Immune Deficiency Syndrome (AIDS), and impact. The study found that both the infected and affected employees were affected physically and psychologically by HIV/AIDS in different ways. It was indicated that the impact was also experienced in different ways. The impact depended on the type of a job of an infected employee. Employees were found to be at various stages and relapsing to and from backward stages, most of the time. As a final product of the applied research used for this study, some guidelines to make a difference to the impact are proposed. Proposals constitute future broad guidelines with regard to HIV/AIDS services to be provided by the Employee Assistance Professional and management, and the support to be provided to both the HIV infected and affected employees. / Dissertation (MSD (EAP))--University of Pretoria, 2005. / Social Work and Criminology / unrestricted

Human immunodeficiency virus (HIV) is currently the most significant infectious pathogen and the causative agent of acquired immune deficiency syndrome (AIDS). Unfortunately, due to lack of resources, delivery of antiretroviral therapy (ART) to countries where they are most needed, such as South Africa, Botswana, Lesotho, Malawi and Swaziland, is limited and inefficient. Moreover, the short supply and high cost of antiretroviral drugs have caused researchers to turn to plants as prospective therapies in the search for alternative anti-HIV or immunomodulatory compounds. In an African context, traditional medicines are of great importance, not so much as an alternative to treatment, but in many cases as the only source of treatment. There are various South African plants used medicinally which possess phytochemical constituents that target certain mediators of inflammation and the immune system. In African regions where patients do not have access or financial capability to obtain conventional antiretroviral treatment, traditional herbal medicines are used as primary treatment of HIV/AIDS, regardless of the fact that the safety, toxicity and efficacy of these products are not yet fully understood and that a risk for adverse effects exists. Hypoxis hemerocallidea Fisch&C. A. Mey. (Hypoxidaceae) as well as Sutherlandia frutescens L. R. Br. (Leguminosae) have various effects on the immune system and due to claims about their immune boosting properties, they are two of the most common African herbal compounds being used for HIV management in South Africa. In this study, the immune modulating properties of H. hemerocallidea and S. frutescens were investigated in order to determine whether anectodal claims made about these plants could be supported. Differentiated THP-1 and U937 macrophages were treated with aqueous extracts of H. hemerocallidea and S. frutescens as well as with solutions of compound standards reputedly isolated from these plants such as beta-sitosterol, found in H. hemerocallidea, canavanine, pinitol and gammaaminobutyric acid (GABA) which are present in S. frutescens Cytotoxicity of the test compounds was determined using the 3-(4,5-dimethylthiazol- 2-yl)-2,5-dephenyl tetrazolium bromide (MTT) assay. Antioxidant capacity was assessed using the Trolox equivalence antioxidant capacity (TEAC) and Oxygen radical antioxidant capacity (ORAC) assays. Determination of prostaglandin E2 (PGE2) concentration in treated THP-1 and U937 cell culture supernatants was performed by ELISA. Concentrations of cytokines (IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, TNF-á and IFN-ϒ) in treated THP-1 and U937 cell culture supernatants were determined by flow cytometry. Curcumin, a well-known immunomodulatory compound, was used as a positive control. Results of cytotoxicity assessments showed that H. hemerocallidea (0.1 – 1.9 mg/ml), S. frutescens (0.1 – 1.6 mg/ml), beta-sitosterol (0.2 – 25 ìM), canavanine, pinitol and GABA (1.5 – 200 ìM) were not cytotoxic to THP-1 and U937 macrophages and had cytotoxicity profiles comparable to that of the positive control, curcumin (0.8 - 25 ìM). The TEAC and ORAC assays showed different results in the antioxidant capacities of the test compounds. The purported antioxidant activity of H. hemerocallidea was confirmed by the TEAC assay with antioxidant effects equivalent to 0.2 mg/ml Trolox. Canavanine showed antioxidant activity equivalent to approximately 0.17 mg/ml Trolox and comparable to that of curcumin in the ORAC assay, suggesting its involvement in the inhibition of peroxyl radical-induced oxidation. Flow cytometry results showed that curcumin (20 ìg/ml and 10 ìg/ml) and beta-sitosterol (25 ìg/ml and 12.5 ìg/ml) reduced IL-1â and IL-8 production and significantly (p<0.05) decreased the production of TNF-á. This suggests that betasitosterol could indeed possess anti-inflammatory properties, with effects comparable to the known anti-inflammatory effect of curcumin in terms of cytokine profiles. Beta-sitosterol (25 ìg/ml) and pinitol (50 ìg/ml) significantly (p<0.001) decreased extracellular PGE2 levels in U937 macrophages by 233.4 pg/ml and 281.7 pg/ml, respectively and were the only two compounds showing greater reductions in PGE2 than curcumin. In conclusion, results of this study do not provide enough evidence to support all anecdotal claims about the ‘immune boosting’ properties of S. frutescens and H. hemerocallidea, but the compounds canavanine, beta-sitosterol and pinitol were found to have modulatory effects on certain aspects of the immune system. / Dissertation (MSc)--University of Pretoria, 2011. / Pharmacology / unrestricted

Philosophiae Doctor - PhD / Background: The Human Immunodeficiency virus (HIV) has become a global public health challenge amid the growing concern of adolescent risky sexual behaviour, influenced by biological and psycho-social factors. There is an increasing demand for adolescent sexual risk reduction interventions, especially in sub-Saharan Africa which remains the hub of HIV epidemic worldwide. Sport-based HIV prevention programme has been identified as one of the interventions, in addition to other approaches to provide young people with appropriate HIV knowledge and skills to either delay or reduce risk-taking behaviour. Despite the potential of sport-based programme for sexual risk reduction, there is limited information on how to adapt it to meet adolescent needs in terms of design, contents, and delivery. This information is necessary to provide sufficiently strong evidence to support widespread implementation of sport-based programme, especially in rural African schools. Therefore, the study aimed to measure the impact of a sport-based HIV prevention intervention in the reduction of HIV related sexual risk behaviour among rural high school learners aged 13-18. Method: The overall study design was a concurrent mixed method, utilizing both the quantitative and qualitative approach. The population for the quantitative and the qualitative studies was made up of two high schools in a predominantly “Coloured” community in Ceres. Two classes each were randomly selected from grades 8-10 in both intervention and control school. The intervention was developed through a process of focus group discussions with the Grassroot Soccer (GRS) staff and it was guided by the Social Cognitive Theory. The intervention was delivered to grade 8-10 learners by GRS peer facilitators using the GRS generation skillz curriculum that consists of 12-week sessions in the intervention school. Quantitative data were analysed with multivariate statistical techniques and qualitative data with thematic analysis approach. Results: The data that assessed the behavioural and protective factors to understand why learners in rural schools engage in risky sexual behaviour showed that about 27.2% of the learners reported being sexually active. Of the sexually active learners, 48.7% reported engaging in sex by 14 years or younger and nearly 42.2% reported multiple sexual partners with significant higher proportion of boys than girls. Nearly 55.2% of the sexually active learners reported irregular condom use and 46.3% did not use a condom at the last sexual encounter. The majority of the learners (87%) did not know their HIV status. Being male (OR = 6.60;95% C I = 1.62 – 26.84) and peer influence (OR = 3.01; 95% CI = 1.97-4.60) were the strongest predictors of reporting sexual intercourse and early sexual activities before the age 15 respectively. Though the knowledge of HIV was low, those with greater knowledge of HIV were more likely to use a condom at last the sexual encounter (OR = 1.22; 95% C I =1.03-1.44). The learners who participated in sport-based intervention were 1.43times likely to report higher self-efficacy to refuse sex compared to the control group (OR = 1.43; 95% C.I =1.07-1.92).The process evaluation indicated that the sport-based intervention was well received among the learners as it gave them free space to freely express themselves. Conclusion: The findings have shown that sport-based intervention can be successfully implemented in school and is a promising approach to reduce risks associated with risky sexual behaviour in learners. However, the quality of the programme delivery was hampered by irregular session‟s schedule and language of instruction. The process suggests for a longer exposure period and because of social-cultural diversity, learners must be provided with the ownership of the programme in schools.

Thesis (MPH.) -- University of Limpopo (Medunsa Campus), 2011 / INTRODUCTION: The human immune deficiency virus (HIV) leads to the acquired immune deficiency syndrome (AIDS). AIDS was first identified in the 1980’s and since then has spread globally causing one of the most dreaded pandemics of modern time. The issue of stigma is very important in the battle against HIV/AIDS as it affects attendance at health centres for obtaining ARV and regular medical check-ups, adherence of patients to ARV treatment. The fear of stigma further helps to fuel a culture of secrecy, silence, ignorance, blame, shame and fear of victimization. AIM: The aim of this study was to determine if there was any external stigmatization of HIV positive patients by health care workers (HCWs) at King Edward VIII Hospital. OBJECTIVES: To determine if the knowledge of HCWs regarding HIV/AIDS and its transmission affect the way they supply a service towards HIV positive patients at King Edward VIII Hospital and to determine the comfort level and the attitude of the HCWs in rendering care to a HIV positive patient. METHODOLOGY: This was a cross sectional survey where data was collected using an anonymous selfadministered structured questionnaire with closed ended questions on personal and professional characteristics, disease knowledge, and discriminatory practices such as attitudes and comfort levels towards people living with HIV/AIDS (PLWHA). A total of three hundred and thirty four HCWs from different units at the King Edward VIII hospital participated in this study. FINDINGS Overall the HCWs have an above average knowledge about HIV/AIDS and its transmission with only 1.8% scoring below average in the knowledge questions regarding HIV and its transmission, although some knowledge gaps were identified regarding occupational exposure risks. Evidently from the results is that HCW with higher levels of education are more knowledgeable on issues relating to HIV/AIDS. The implication is that a HCW with a better education is better equipped with the cognitive knowledge to deal with HIV/AIDS, highlighting the importance of education related to external stigmatization. Even though HCWs were knowledgeable about HIV/AIDS most still felt uncomfortable in performing some occupational duties on PLWHA like assisting a woman in labour and performing invasive surgical operations. Most of the HCWs showed a positive attitude towards PLWHA believing that they are not to be blamed for their condition but that individuals in the community who are perceived to be promiscuous men or women are the ones responsible for the spread of HIV/AIDS. Procedures like patients being tested without their consent and patients required to do a HIV/AIDS test before surgery that could be perceived as stigmatization have been observed in King Edward VII hospital. Patient confidentiality is also compromised in that gossiping by HCWs about the HIV/AIDS results of patients has been noted. Fortunately a significant number of HCWs are willing to report their colleagues to a higher authority if any form of stigmatization or discrimination towards PLWHA is seen at King Edward VIII Hospital. CONCLUSION Although the knowledge, attitude and comfort of the HCWs at King Edward VIII Hospital was above average continuing medical education and continuing professional development should be mandatory in the management of HIV/AIDS so that HCWs can have the needed knowledge to keep up with the changing world of HIV/AIDS medicine and also about universal precautions to take so as to reduce occupational exposures. Psychological support to the HCW is needed in dealing with PLWHA so that patients can be provided with quality and compassionate care irrespective of their HIV/AIDS status as this will eventually help in the reduction of stigma.

Nearly half of all HIV-positive individuals present with some form of HIV-associated neurocognitive disorder (HAND). The experiments described in this thesis examined the structural changes that occur in the brain as a result of HIV infection. While previous work has established that HIV targets the basal ganglia and fronto-striatal systems and impacts cortical and white matter pathways, it was unknown whether these changes occur in the absence of HAND. The studies described here focused on cognitively asymptomatic HIV+ individuals (CAHIV+) without HAND as determined by widely accepted neuropsychological performance guidelines. Experiment 1 utilized diffusion tensor imaging (DTI) to examine HIV-associated alterations in white matter (WM) fractional anisotropy (FA) in the absence of HAND in 23 HIV+ individuals and 17 control participants (HIV-) matched for age, education, and verbal IQ. The hypothesis was that CAHIV+ participants would show lower FA values than HIV- in the corpus callosum, frontotemporal, and parietal regions of interest (ROIs). CAHIV+ individuals demonstrated higher FA in the frontotemporal region and posterior corpus callosum, but lower FA in parietal WM relative to HIV- individuals. Experiment 2 utilized structural MRI to compare cortical thickness in 22 CAHIV+ individuals and 19 control participants (HIV-) matched for age, education, and verbal IQ. The hypothesis was that CAHIV+ participants would have thinner frontal, temporal, and parietal regions than HIV- participants. Reduced cortical thickness measures were identified in the cingulate and superior temporal gyri, with increased cortical thickness measures in the inferior occipital gyrus, for HIV+ participants compared to HIV-. Experiment 3 examined the relationship between the structural alterations identified in Experiments 1 and 2, neuropsychological performance on tests sensitive to HAND identification, and immunological characteristics in 30 HIV+ participants and 28 HIV- control participants. As hypothesized, regional FA values, cortical thickness, and viral load were related to neuropsychological composite scores for CAHIV+, but not HIV-. Together, results from these three studies suggest that regional FA and cortical alterations identified in CAHIV+ patients may contribute to the cognitive deficits often seen in later stages of HIV disease.