Propriedades de estado sólido estão diretamente relacionadas ao desempenho de um fármaco. Entre todas as propriedades físicas e químicas dependentes da fase cristalina de um fármaco, estabilidade e solubilidade são as que mais alteram sua biodisponibilidade. Neste sentido, a engenharia de cristais moleculares é uma estratégia para aperfeiçoar as propriedades de estado sólido relacionadas às eficácias dos fármacos. Neste trabalho, nove novas formas cristalinas de fármacos antirretrovirais inibidores nucleosídeos de transcriptase reversa, a saber, lamivudina, zalcitabina e didanosina, foram preparadas e suas estruturas cristalinas foram elucidadas por difração de raios X por monocristal. Parte das modificações cristalinas preparadas foi também caracterizada por microscopia eletrônica de varredura, difração de raios X por pó, espectroscopia vibracional no infravermelho e Raman, calorimetria exploratória diferencial e termogravimetria. As solubilidades aquosas e purezas das modificações cristalinas de lamivudina preparadas como amostras monofásicas foram determinadas por espectrofotometria de absorvância no ultravioleta e cromatografia líquida de alta eficiência, respectivamente. A solubilidade de lamivudina nas modificações cristalinas preparadas pode ser tanto aumentada quanto reduzida quando comparada com a solubilidade da fase cristalina do fármaco incorporada em formulações farmacêuticas. As solubilidades foram também correlacionadas às características estruturais e calorimétricas, o que permitiu o estabelecimento de relações entre estrutura/energia de rede cristalina e propriedade de estado sólido. Ainda, duas modificações cristalinas de lamivudina, em que moléculas do fármaco estão pareadas através de seus fragmentos de citosina, sendo estes pares helicoidalmente sobrepostos, mimetizando uma estrutura polimérica de ácido desoxirribonucléico, revelaram que nucleosídeos têm a informação estrutural necessária para arquitetar duplas hélices de ácidos nucléicos. / Solid state properties are directly related to drug performance. Among all physical and chemical properties dependent on the crystal phase of a drug, stability and solubility are the main ones that alter its bioavailability. In this way, molecular crystal engineering is a strategy to improve solid state properties of drugs related to their efficacies. In this work, nine new crystal forms of antiretroviral nucleoside reverse transcriptase inhibitor drugs, namely, lamivudine, zalcitabina and didanosine, were prepared and their crystal structures were elucidated by single crystal X-ray diffraction. Some of the prepared crystal modifications were also characterized by scanning electron microscopy, powder X-ray diffraction, infrared and Raman vibrational spectroscopy, differential scanning calorimetry and thermogravimetry. The water solubilities and purities of the lamivudine crystal modifications prepared as monophasic samples were determined by ultraviolet absorbance spectrophotometry and high performance liquid chromatography, respectively. The solubility of lamivudine in the prepared crystal modifications can be either increased or decreased when compared to the solubility of the drug crystal phase incorporated into pharmaceutical formulations. The solubilities were also correlated to calorimetric and structural features, which allowed the establishment of relationships between crystal lattice energy/structure and solid state property. In addition, two crystal modifications of lamivudine, in which drug molecules are paired through their cytosine fragments, being these pairs helically stacked, mimicking a polymeric structure of deoxyribonucleic acid, have revealed that nucleosides possess the structural information necessary to assemble double stranded helices of nucleic acids.

Thesis (MPH.) -- University of Limpopo, 2015 / The success of antiretroviral therapy for HIV infection through widespread and resounding has been limited by inadequate adherence to its unforgiving regimens especially over a long term. While health care professionals may not be able to predict adherence, they can help overcome barriers to adherence and take steps to improve it. The aim of the study was to explore and describe the strategies that are utilised by professional nurses in the primary health care facilities regarding adherence to antiretroviral therapy, Capricorn District, Limpopo Province, South Africa. A qualitative research approach was used to describe the strategies that are utilised by professional nurses in the primary health care facilities in the Capricorn District Limpopo Province, referring to Mankweng Hospital. The descriptive qualitative design was used. Unstructured interviews were used to collect data until saturation was reached. Informed consent was obtained prior the data collection. The data was analysed qualitatively using Tesch’s open coding method. 18 (eighteen) professional nurses working in the primary health care facilities participated in the study. The findings revealed that the strategies utilised by professional nurses in the primary health care facilities to improve adherence to ART were described. Information and education, health worker and adherence guidelines, use of adherence partner or treatment buddy, addressing religious beliefs, communication skills, community mobilisation and continuous counselling, were the strategies that were utilised by professional nurses in the primary health care facilities to improve adherence of patients to ART.

PhD. (Department of Chemical Engineering, Faculty of Engineering and Technology), Vaal University of Technology. / Human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) causes morbidity and mortality in infected patients. These epidemics are significantly reduced and treated globally with antiretroviral drugs (ARVDs). However, the eventual disposal of the ARVDs, either by excretion or otherwise, enables them to end up as emerging hazardous contaminants in our environment. Of all the available methods to remove ARVDs from our water bodies, electrochemical methods are reckoned to be one of the most effective. As a result, it is imperative to acknowledge the interactive behavior of these pharmaceuticals on the surface of the electrode. In this study, iron nano-particles were deposited on the carbon cloth electrode by electrodeposition using chronoamperometry techniques. The synthesized electrode was characterized using scanning electron microscopy (SEM), energy-dispersive x-ray spectroscopy (EDX), and x-ray photoelectron spectroscopy (XPS) microanalysis. The electrochemical characterization of the material was also carried out using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The electrode's electrocatalytic activity toward the generation of hydrogen peroxide (H2O2) through a two-electron oxygen reduction reaction was assessed. Furtherance to this is the electrochemical degradation of nevirapine (NVP), lamivudine (LVD), and zidovudine (ZVD) in wastewater as a pharmaceutical model compound for organic pollutants in 50 mM K2SO4 electrolyte at a pH of 3. The SEM and EDX analysis showed the formation of iron nanoparticles within the matrix structure of the carbon cloth (CC) electrode. The XPS enlightened the presence of oxygen functional groups in the electrode's structure. EIS results are indicative that the modified electrode has a decreased charge transfer resistance (Rct)value as compared to the bare CC electrode. On the other hand, the CV result fosters good conductivity, enhanced current and large surface area of the modified electrode. More active and anchor sites were discovered on the iron-supported CC electrode which resulted in higher catalytic activity for the generation and accumulation of H2O2. The concentrations of “in-situ” generated H2O2 were found to be related to the current density supplied to the device after quantification. Although the accumulated H2O2 concentration appears to be low, it's possible that side reactions depleted the amount of H2O2 produced. As a result, the oxygen reduction reaction (ORR) through 2e- has a higher electrocatalytic activity with the improved iron assisted CC electrode than bare CC electrode. The electrochemical degradation studies conducted with the modified CC electrode by electro-Fenton process show a decrease in the initial ARVDs concentration (20 mg/L) as compared with the bare electrode. Their rate constants were 1.52 x 10-3 mol-1min-1 for ZVD, 1.20 x 10-3 mol-1min-1 for NVP and 1.18 x 10-3 mol-1min-1 for LVD. The obtained removal efficiencies indicate that the iron nanoparticle in the synthesised improves the degradation efficiency.

A qualitative study following a phenomenological approach was undertaken to explore voluntary counselling and testing nurses' perception of educating HIV+ people about ARVs. Non-probability convenience sampling was used and in-depth semi-structured face-to-face interviews were conducted to collect data from 12 participants. The most important results were:  The need for extensive education on ARVs since it is a new technology used to curb the infection therefore clients need the information in order to use them effectively.  Stumbling blocks encountered when educating HIV+ people about the drugs. The problems are mainly due to the nurses lack of current knowledge about the drugs; patients' low economic status; severe side effects; difficulties in behaviour change; poor quality of life on ARVs and medical terminology.  Inability of clients to comply to the regimen because of severe side effects, complex regimen, lack of support from family and friends, lack of motivation, depression, cultural beliefs, lack of knowledge on how to use them and financial constraints.  Challenges for continuous education because of current nursing shortage, negative attitudes of some nurses, demotivation and inadequate funding for such activity. Recommendations include provision of continuing education and the incorporation of ARV therapy knowledge in the basic nursing curriculum in nursing education. / Health Studies / MA (HEALTH STUDIES)

The purpose of the study was to evaluate the IMB skills model for its relevance to the Ethiopian context. According to the model, adherence-related information and motivation work through adherence-related behavioural skills to affect adherence to ART. Quantitative, analytical, observational, cross-sectional, institution-based study was conducted to evaluate the model by assessing those patients who have and do not have the right information, motivation, and behavioural skills whether they have or do not have good adherence to ART. Data was collected using structured questionnaires where a total of 400 randomly selected participants provided data on adherence-related information, motivation and behavioral skills as well as adherence behavior per se. Data was analysed using the Statistical Package for Social Sciences (SPSS) version 20.0. Both descriptive and inferential statistics used in the study. Only 90.75 % of the total sample population reported ART adherence rate of more than or equal to 95% in this study. Free and restricted model tests, through bivariate and multivariate analyses, used to assess the propositions of the IMB model of ART adherence and provided support for the interrelations between the elements proposed by the model. The study has supported the applicability of the IMB model of adherence to the Ethiopian context highlighting its application in adherence-promotion intervention efforts. The findings revealed 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 ART adherence behaviour. / Health Studies / D. Litt. et. Phil. (Health Studies)

A qualitative study following a phenomenological approach was undertaken to explore voluntary counselling and testing nurses' perception of educating HIV+ people about ARVs. Non-probability convenience sampling was used and in-depth semi-structured face-to-face interviews were conducted to collect data from 12 participants. The most important results were:  The need for extensive education on ARVs since it is a new technology used to curb the infection therefore clients need the information in order to use them effectively.  Stumbling blocks encountered when educating HIV+ people about the drugs. The problems are mainly due to the nurses lack of current knowledge about the drugs; patients' low economic status; severe side effects; difficulties in behaviour change; poor quality of life on ARVs and medical terminology.  Inability of clients to comply to the regimen because of severe side effects, complex regimen, lack of support from family and friends, lack of motivation, depression, cultural beliefs, lack of knowledge on how to use them and financial constraints.  Challenges for continuous education because of current nursing shortage, negative attitudes of some nurses, demotivation and inadequate funding for such activity. Recommendations include provision of continuing education and the incorporation of ARV therapy knowledge in the basic nursing curriculum in nursing education. / Health Studies / MA (HEALTH STUDIES)

The purpose of the study was to evaluate the IMB skills model for its relevance to the Ethiopian context. According to the model, adherence-related information and motivation work through adherence-related behavioural skills to affect adherence to ART. Quantitative, analytical, observational, cross-sectional, institution-based study was conducted to evaluate the model by assessing those patients who have and do not have the right information, motivation, and behavioural skills whether they have or do not have good adherence to ART. Data was collected using structured questionnaires where a total of 400 randomly selected participants provided data on adherence-related information, motivation and behavioral skills as well as adherence behavior per se. Data was analysed using the Statistical Package for Social Sciences (SPSS) version 20.0. Both descriptive and inferential statistics used in the study. Only 90.75 % of the total sample population reported ART adherence rate of more than or equal to 95% in this study. Free and restricted model tests, through bivariate and multivariate analyses, used to assess the propositions of the IMB model of ART adherence and provided support for the interrelations between the elements proposed by the model. The study has supported the applicability of the IMB model of adherence to the Ethiopian context highlighting its application in adherence-promotion intervention efforts. The findings revealed 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 ART adherence behaviour. / Health Studies / D. Litt. et Phil. (Health Studies)

Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Bc. Michaela Jahodová Supervisor: PharmDr. Lukáš Červený, Ph.D. Title of diploma thesis: In vitro and ex vivo study of drug-drug interactions of antiretrovirals on intestinal ATP-binding drug transporters The absorption of orally administered drugs takes place especially in the intestine, where it can affect by the activity of drug's ABC transporters located on the apical membrane of the intestinal epithelium. Study of drug interactions in intestinal ABC transporters is essential to ensure effective and safe pharmacotherapy. Testing of bi- directional transport on Caco-2 cells is generally the preferred method for in vitro evaluation of substrates and inhibitors of ABC transporters. Drawbacks of the Caco-2 model increase the need and necessity to introduce new models. A great potential is the involvement of ex vivo methodologies in the human or rat intestine. The aim of the work was to introduce an in vitro methodology using the Caco-2 cell monolayer and the ex vivo methodology of precision-cut rat intestinal slices. By the bi-directional transport method, we analyzed drug interactions of the model substrate P-gp and BCRP Rhodamine 123 (RHD123) and clinically-used tenofovir...

The purpose of the study is to investigate and identify the factors that affect utilisation of prevention mother to child transmission of HIV services and propose measures to promote utilisation of services by HIV positive pregnant women in Onitsha, Anambra State, Nigeria. Mother-to-child transmission of HIV accounts for over 90% of infections in children under 15 years. Infected pregnant women can pass on the infection to their babies during pregnancy, delivery or through breastfeeding. There are effective interventions now reduce of the infection to the baby. However some infected women still do not avail themselves of these services due to several reasons. A quantitative descriptive study, using the Health Belief Model as the conceptual framework was used to conduct the research. A structured interview schedule was used to interview 102 pregnant women at two health facilities in Onitsha, Anambra state, Nigeria. The findings from the study reveal that majority of the respondents knew about HIV transmission but not about ways the infection can be transmitted from mother-to-child. The respondents recognise that HIV/AIDS is a very serious threat in Nigeria and the study site and were of the opinion that all pregnant women should know their HIV status. The attitude of health care workers and fears about disclosure of HIV status to others was a setback. Revealing their status to the spouse was feared.

Antiretroviral drugs were introduced into Uganda during the past decade and have revolutionised the treatment of AIDS. However, in as much as success was recorded, new challenges emerged. One such challenge was the continued use of condoms. This study investigated existing knowledge, attitudes and practices of condom use in a time of highly active antiretroviral therapy in a rural area. A quantitative, cross sectional design, with probability sampling form the general population was utilised. A self-designed questionnaire was used to collect data which was then analysed at the descriptive statistics level. The results indicated that: knowledge of HIV, its transmission, condoms and antiretroviral drugs were high among the respondents; condom acceptance and use were low; and respondents would not intentionally engage in unprotected sexual intercourse because of availability of ARVs. However it was acknowledged that some people taking ARVs have engaged in risky sexual behaviours that would expose others to infection. / Health Studies / M.A. (Public Health)