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Submitted in complete fulfilment for the Degree of Doctorate of Technology (Biotechnology)--Durban University of Technology, 2013. / South Africa has the largest number of people infected with HIV/AIDS. It also has more than 30 000 species of plants and many of these have a long tradition of medicinal use. It is highly likely that the treatment for HIV will come from this traditional knowledge. The need for effective preventative and therapeutic agents for HIV remains an urgent global priority. The aim of this study was to screen selected South African medicinal plants for anti-HIV activity and to identify and characterise an active compound from a plant that can be used for HIV treatment. The aqueous and methanolic extracts of the roots, leaves, flowers and stems of thirty eight plant species (108 extracts) were screened for anti-HIV activity. The plants which had anti-HIV activity were further screened for anti-reverse transcriptase activity. Thirty-two extracts exhibited varying degrees of anti-HIV activity. Cleome monophylla, Dichrostachys cinerea and Leonotis leonurus aqueous leaf extracts had anti-HIV-1 reverse transcriptase activity. The aqueous extracts of D. cinerea showed the best anti-HIV activity with a Selectivity Index of 43.5 and significant anti-HIV-1 reverse transcriptase activity. Crude phytochemical screening of D. cinerea showed that it had tannins, saponins, flavonoids and alkaloids but did not contain any phlobatannins, terpenoids, steroids or phenols. D. cinerea displayed a high degree of free radical scavenging activity with an IC50 of 25 μg/ml, therefore the anti-HIV activity could be attributed to the flavonoids present in the plant. Bio-guided fractionation was used to isolate and purify the active compound from the D. cinerea extract. Compounds were isolated by thin layer chromatography and were tested for anti-HIV-1 and anti-reverse transcriptase activity. From these results the active compound was identified, and purified using preparative TLC. The active compound was characterised by High Performance Liquid Chromatography, Ultraviolet-visible spectrophotometry, and Ultra Performance liquid chromatography coupled to MS/MS. Structural elucidation was performed using Nuclear Magnetic Resonance. From these results, it was deduced that the compound isolated from D. cinerea was a catechin. In this study we show that the catechins present in D. cinerea are responsible for the anti- HIV-I activity and inhibits the reverse transcriptase activity which is a key factor in the progression of HIV. Potentially, these results can be used to develop a new drug for the treatment of HIV or as a cost effective therapeutic agent in treating HIV-infected individuals with oxidative stress. / National Research Foundation

Thesis (MFamMed)--Stellenbosch University, 2015. / ENGLISH SUMMARY: Background: Sub Saharan Africa is home to approximately two thirds of the world’s population of HIV positive individuals. In view of the socioeconomic challenges of the region governments have provided antiretroviral therapy free to improve chances of survival among patients. However, adherence to antiretroviral therapy is recognised as more important in predicting patient survival. Aim: The study aimed to describe the prevailing factors that influence adherence to antiretroviral therapy. Methods: The study design was carried out using three methods of data collection. Focus group discussions, semi structured interviews and a questionnaire format. Setting: This study has been conducted among adult patients attending the Dora Nginza Hospital Adult wellness clinic. Results: The methods highlighted factors that influence antiretroviral therapy revealing psychosocial factors – lack of family support, not wanting to take medicines in front of people outside the home; patient factors – co morbidities that disturb patient adherence to therapy, a lack of trust in the patient-care giver relationship, fear of the drug side effects; socioeconomic factors – patients’ inability to afford food or transport costs to clinic appointments. In the semi structured interviews, 25% of patients self reported on poor adherence while in the questionnaire 5% of patients reported poor adherence. In assessing the effect of adherence to therapy on CD4 count and viral load there was a general increase in CD 4 count and a drop in viral load indicating clinical improvement in patients on therapy. Recommendation: There is a need for clinicians developing a health relationship with patients to facilitate adherence. The interventions designed to help patients in adherence to therapy should involve the patients in question in the designing of these interventions. Conclusion: Adherence monitoring is an important aspect of managing patients on antiretroviral therapy. The factors highlighted are similar to findings of other studies in similar contexts i.e. resource poor settings. / AFRIKAANSE OPSOMMING: Opsomming nie beskikbaar.

The objective of this study was to assess levels of HAART adherence and factors affecting it. An observational, analytic, cross-sectional and quantitative study using IMB model was conducted on a randomly selected 349 HIV/AIDS patients on a HAART regimen. Data collection was done by interviewing respondents using a structured questionnaire. Both descriptive and inferential statistics used in the study. Only 80.2% of the total sample population reported a HAART adherence rate of more than or equal to 95% in this study. The findings highlight the need for on-going educational, informational and other interventions to address the knowledge, motivation and adherence behavioural skills of patients in order to improve the current levels of HAART adherence behaviour. The study also suggested the need for research into objective measures of adherence as well as longitudinal studies on adherence behaviour because strict adherence to treatment is a long-term process and not a one-time activity. / Health Studies / M.A. (Public health)

Na prática fisioterapêutica utilizam-se diversas técnicas de eletroterapia com finalidades antissépticas e bactericidas. Porém, poucos estudos são encontrados sobre a ação de gerador de alta frequência no tratamento de enfermidades causadoras de contaminação/infecção, como feridas crônicas. Contudo, geradores de alta frequência são conhecido por seu efeito bactericida e antisséptico, graças à produção de ozônio na superfície onde é aplicado. Tendo em vista que o gerador de alta frequência apresenta baixo custo, fácil manuseio e ação potencializadora do processo cicatricial, por meio da sua ação bactericida, a presente dissertação teve como objetivo avaliar o efeito antimicrobiano de gerador de alta frequência sobre as bactérias Staphylococcus aureus, Pseudomonas aeruginosa e Acinetobacter baumannii. Realizou-se testes de tamanho de halo de inibição; contagem de unidades formadoras de colônia, citometria de fluxo usando o kit Live/Dead® para verificar integridade da membrana e rodamina 123 para avaliar o estresse oxidativo e avaliação da temperatura. Conclui-se que o gerador de alta frequência apresenta ação bactericida, sendo, que o tempo e a frequência comportam-se de forma dependente, sua ação é dose-dependente e age de forma mais expressiva em bactérias Gram-negativas, Sua utilização não causa aumento da temperatura local, apenas no eletrodo de vidro e a produção de radicais livres aumenta com o tempo de exposição ao gerador de alta frequência (833Hz), enquanto a viabilidade celular decresce. / Submitted by Ana Guimarães Pereira (agpereir@ucs.br) on 2016-12-09T17:12:27Z No. of bitstreams: 1 Dissertacao Gabriela Manosso Bampi.pdf: 1053473 bytes, checksum: 47b9df5694f5409de46618b2d0f7c98b (MD5) / Made available in DSpace on 2016-12-09T17:12:27Z (GMT). No. of bitstreams: 1 Dissertacao Gabriela Manosso Bampi.pdf: 1053473 bytes, checksum: 47b9df5694f5409de46618b2d0f7c98b (MD5) Previous issue date: 2016-12-09 / Conselho Nacional de Desenvolvimento Científico e Tecnológico / In the physiotherapy practices, various electrotherapy techniques are used with antiseptic and antibacterial purposes; however, few studies are found about the action of high-frequency generator in the treatment of diseases causing contamination/infection, such as chronic wounds; nevertheless, the high-frequency generator is known for its antiseptic and bactericidal effect by producing ozone at the surface where it is applied. Considering that the high-frequency generator is inexpensive, easy handling and potentiating action of the healing process through their bactericidal action, this thesis aims to evaluate the antimicrobial effect of highfrequency generator on bacteria of the genus Staphylococcus aureus, Pseudomonas aeruginosa and Acinetobacter baumannii. To analyzed the action of highfrequency generator the following tests are realizes: inhibition zone size; counting colony forming units, flow cytometry using the kit Live / Dead® to verify membrane integrity and rhodamine 123 to assess oxidative stress and temperature evaluation. Concluding that the high-frequency generator has bactericidal action, time and frequency behave as dependents, revealing its action is dose-dependent and acts more significantly in Gram-negative bacteria. Its use does not cause local temperature increase, only the glass electrode and the free radical production increases with time of exposure to the high-frequency generator (833Hz), while cell viability decreased.

Na prática fisioterapêutica utilizam-se diversas técnicas de eletroterapia com finalidades antissépticas e bactericidas. Porém, poucos estudos são encontrados sobre a ação de gerador de alta frequência no tratamento de enfermidades causadoras de contaminação/infecção, como feridas crônicas. Contudo, geradores de alta frequência são conhecido por seu efeito bactericida e antisséptico, graças à produção de ozônio na superfície onde é aplicado. Tendo em vista que o gerador de alta frequência apresenta baixo custo, fácil manuseio e ação potencializadora do processo cicatricial, por meio da sua ação bactericida, a presente dissertação teve como objetivo avaliar o efeito antimicrobiano de gerador de alta frequência sobre as bactérias Staphylococcus aureus, Pseudomonas aeruginosa e Acinetobacter baumannii. Realizou-se testes de tamanho de halo de inibição; contagem de unidades formadoras de colônia, citometria de fluxo usando o kit Live/Dead® para verificar integridade da membrana e rodamina 123 para avaliar o estresse oxidativo e avaliação da temperatura. Conclui-se que o gerador de alta frequência apresenta ação bactericida, sendo, que o tempo e a frequência comportam-se de forma dependente, sua ação é dose-dependente e age de forma mais expressiva em bactérias Gram-negativas, Sua utilização não causa aumento da temperatura local, apenas no eletrodo de vidro e a produção de radicais livres aumenta com o tempo de exposição ao gerador de alta frequência (833Hz), enquanto a viabilidade celular decresce. / Conselho Nacional de Desenvolvimento Científico e Tecnológico / In the physiotherapy practices, various electrotherapy techniques are used with antiseptic and antibacterial purposes; however, few studies are found about the action of high-frequency generator in the treatment of diseases causing contamination/infection, such as chronic wounds; nevertheless, the high-frequency generator is known for its antiseptic and bactericidal effect by producing ozone at the surface where it is applied. Considering that the high-frequency generator is inexpensive, easy handling and potentiating action of the healing process through their bactericidal action, this thesis aims to evaluate the antimicrobial effect of highfrequency generator on bacteria of the genus Staphylococcus aureus, Pseudomonas aeruginosa and Acinetobacter baumannii. To analyzed the action of highfrequency generator the following tests are realizes: inhibition zone size; counting colony forming units, flow cytometry using the kit Live / Dead® to verify membrane integrity and rhodamine 123 to assess oxidative stress and temperature evaluation. Concluding that the high-frequency generator has bactericidal action, time and frequency behave as dependents, revealing its action is dose-dependent and acts more significantly in Gram-negative bacteria. Its use does not cause local temperature increase, only the glass electrode and the free radical production increases with time of exposure to the high-frequency generator (833Hz), while cell viability decreased.

M.A. (Public Management and Governance) / This study starts with an introduction and background, and this is followed by a statement of the research problem, research rationale, research objectives, research design, research methodology and the data collection methods. A list of acronyms will be provided, as well as an overview of chapters, conclusions, and acknowledgements. “Around 5.7 million in 2009 had contracted HIV and AIDS and in the preceding year 250,000 South Africans died due to HIV/AIDS related diseases. All age categories and gender are prone to contracting the disease and the resultant loss of life has had a devastating effect on the workforce. Death due to this disease has caused loss of income and family disintegration” (Sottile 2013:2). In 2010, some 280,000 South Africans died of HIV/AIDS. In the decade up to 2010, between 42% and 47% of all deaths among South Africans were HIV/AIDS-related deaths (Sottile 2013:2). Mlambo et al (2011:1) further say that “The Human Sciences Research Council estimates that 10.9% of all South Africans have HIV/AIDS. Additionally, the Central Intelligence Agency estimates that 310,000 individuals died in South Africa from HIV/AIDS in the year 2009”. A study in 2003 made a comparison on two scenarios, an HIV/AIDS scenario and a no-HIV/AIDS scenario and this was based on the annual growth rates between 2002 and 2015. The finding was that “real growth in GDP would be 0.6% lower than if there were no HIV/AIDS, but per-capita growth in GDP would be 0.9% higher. Growth in population would have been 1.5% lower, and growth of the labour force would be 1.2% lower, but the unemployment rate would be 0.9% lower as well” (Avert.Org 2010:2). Different HIV/AIDS prevention strategies are being implemented in South Africa. The focus in this study is on male medical circumcision (hereafter MMC), which is the removal of all or part of the foreskin on the penis. It can either be performed surgically in hospitals or at initiation schools. Initiation schools perform the procedure as a traditional rite of passage from boyhood to manhood, and this is referred to as traditional male circumcision (TMC). This practice has up till now been performed purely for traditional or religious purposes, but it can no longer be viewed only as such. It should, instead, also be seen as a measure to curb the spread of the HIV/AIDS pandemic. A number of observational studies (which will be referenced later) found that circumcised men had smaller chances of contracting HIV infection compared with uncircumcised men...

The introduction of antiretroviral drugs (ARVs) in 1996 transformed the treatment of HIV and AIDS, improving the quality and greatly prolonging the lives of many infected people. HIV (Human Immunodeficiency Virus) is the virus that is believed to cause AIDS. AIDS (Acquired Immune Deficiency Syndrome) is the collection of illnesses or symptoms that ultimately results in death. Antiretroviral (ARVs) drugs or Highly Active Antiretroviral Therapy (HAART) is the treatment that has been applied to combat the HI virus in a bid to slow down the progression of AIDS and ultimately prolong the life of the infected individual. The study aimed to explore and describe the factors contributing to adherence and non-adherence to ARVs in individuals on treatment. A sample of 81 individuals who have been on ARV and HAART treatment for six months or more was used. The methodology used was exploratory-descriptive and the data obtained was quantitative in nature. A biographical questionnaire and questionnaire with questions aimed at ascertaining the possible factors that contribute to individuals either adhering to or defaulting on their treatment, such as side effects and cost of treatment, was administered. The data obtained was analysed by means of descriptive statistics and frequency counts. The results of the study showed that the sample had a fairly high level of adherence. The factors that could undermine adherence were identified as lack of support, as familial and health provider support acts as a motivator to adhere; substance abuse as it can lead to forgetting to take treatment; unemployment and poverty, as these can lead to an inability to return for follow up clinic visits or failure to have food to take with the pills; and the type of treatment regimen whereby the more complex the treatment is the more likely it is that adherence will be difficult to maintain. Suggestions were made as to future research involving antiretroviral therapy (ART). Finally the limitations as well as the value of the research were outlined.

This study has focused on the synthesis of truncated analogues of the hydroxyethylene dipeptide isosteres, such as Ritonavir®, currently in clinical use as HIV-1 protease inhibitors. The reactions of pyridine-2- and quinoline-2-carbaldehydes with methyl acrylate, in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) or 3- hydroxyquinuclidine (3-HQ) as nucleophilic catalysts, have afforded a series of Baylis- Hillman adducts, acetylation and cyclisation of which have provided access to a series of indolizine-2-carboxylate esters. The carboxylic acids, obtained by base-catalyzed hydrolysis of these esters, have been coupled with various protected (and unprotected) amino compounds using the peptide coupling agent, 1,1’-carbonyldiimidazole (CDI), to afford a series of indolizine-2-carboxamides as indolizine-based truncated Ritonavir® analogues in quantitative yield. Aza-Michael reactions of pyridine-3-carbaldehydederived Baylis-Hillman adducts with various amino compounds have provided access to a range of pyridine-based products as mixtures of diastereomeric aza-Michael products. The assignment of the relative stereochemistry of the aza-Michael products has been established using 1-D and 2-NOESY experiments and computer modelling techniques. Computer modelling studies have also been conducted on selected aza-Michael products using ACCELRYS Cerius2 software, followed by interactive docking into the HIV-1 protease receptor site, using AUTODOCK 4.0. The docking studies have revealed hydrogen-bonding interactions between the enzyme and the synthetic ligands. Saturation Transfer Difference (STD) NMR experiments have also indicated binding of some of the aza-Michael products to the HIV-1 protease subtype C enzyme, thus indicating their binding and possible inhibitory potential.

The project has focused on the preparation of several series of compounds designed as potential HIV-1 integrase inhibitors. Various 2-nitrobenzaldehydes have been reacted with two activated alkenes, methyl vinyl ketone (MVK) and methyl acrylate, under Baylis-Hillman conditions to afford α-methylene-β-hydroxylalkyl derivatives in moderate to excellent yields. The reactions were conducted using the tertiary amine catalysts, 1,4-diazabicyclo[2.2.2]octane(DABCO) or 3-hydroxyquinuclidine (3-HQ) with chloroform as solvent, and yields were optimised by varying the catalyst, reagent concentrations and the reaction time. Reductive cyclization of the Baylis-Hillman adducts via catalytic hydrogenation, using 10% palladiumon-carbon catalyst in ethanol, afforded quinoline and quinoline N-oxide derivatives. In some cases “acyclic” reduction products were also isolated. Reaction of the Baylis-Hillman MVK adducts with HCl, has resulted in effective nucleophilic (SN’) displacement of the hydroxyl group to afford allylic chloride derivatives. Direct substitution of these chloro derivatives by secondary or primary amines, followed by catalytic hydrogenation gave quinoline derivatives containing a 3-aminomethyl substituent. The Baylis-Hillman ester adducts obtained from reaction with methyl acrylate were treated directly with various amines to give diastereomeric conjugate addition products. Reactions with piperazine gave N,N’-disubstituted piperazine products. The piperidine derivatives have been dehydrated to give cinnamate esters in moderate yields. The products, which have all been satisfactorily characterised by elemental (HRMS) and spectroscopic (1- and 2-D NMR) analysis, constitute a “library” of compounds for in silico and in vitro studies as potential HIV integrase inhibitors.