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.

Toxoplasma gondii is a single-celled parasite that has a wide range of hosts including humans. A cross-sectional survey was conducted to investigate T. gondii seroprevalence and associated risk factors in small ruminants, pigs, poultry and cats in the Oliver Reginald Tambo District in the Eastern Cape in South Africa between June 2016 and October 2016. Household-level and animal-level data were collected using a close-ended questionnaire. One sample of each present species was collected in each household. The Toxoreagent ®, Mast Group, United Kingdom, latex agglutination test, was used for T. gondii antibody detection. Positive samples had agglutination patterns at dilutions of 1:64 or greater, except for chickens, whose cut off titre was 1:32. A household was classified as T. gondii seropositive if at least one species tested positive. The study revealed that 78 out of 121 sheep (64.46%), 69 out of 128 goats (53.91%), 36 out of 106 pigs (33.96%), 35 out of 109 cats (32.11%) and 46 out of 137 chickens (33.58%) were seropositive for the parasite. Seropositivity was assessed for association with potential risk factors. Age, location, climate, animal production system, rodent control, cat-feed access and cat faecal disposal were found to be significantly associated with seropositivity using the Chi-Squared test or odds ratio confirmed by the Fisher's exact test. The relatively high seroprevalence of T. gondii detected in this study suggests that the infection T. gondii poses a substantial public health risk through the consumption of infected raw or undercooked meat infected with T.gondii cysts as well as contact with cat faeces infected with T. gondii oocysts. / Dissertation (MSc)--University of Pretoria, 2016. / Veterinary Tropical Diseases / MSc / Unrestricted

HIV and AIDS pandemic have been declining in South Africa. HIV and AIDS affect individuals, families, organizations and the communities at large. While the roll out of the antiretroviral treatment (ART) has brought much excitement and hope to both patients and the health practitioners, it has also brought challenges (Maskew, Macphail, Menez & Rubel, 2007:853). In order for ART to be effective patients need to adhere to antiretroviral treatment, thus adherence is a critical component of ART. Patients who discontinue treatment are at high risk of illness and death because of AIDS related diseases or developing drug resistant virus. With a better understanding of the reasons for defaulting antiretroviral treatment interventions can be designed to improve adherence to antiretroviral treatment. Thus the purpose of this study was to explore the reasons why HIV and AIDS infected patients default antiretroviral treatment because adherence to ART is of utmost important. Within the context of qualitative and applied research the researcher utilized the collective case study design. Semi structured interviewing was used as data collection method to elicit qualitative information on the reasons why patients default ART. The main research question that was put forward to all participants was: What are your reasons for defaulting ART? The participants in this study were patients who have default their ART during 2012. By using systematic sampling fourteen participants from Thekganang ARV Clinic in Seshego District Hospital, Limpopo province, were selected to form a sample for this study. Some conclusions based on the findings were that: The participants were knowledgeable about the basic facts of HIV and AIDS and they had a good understanding about the importance of adherence even though they defaulted their antiretroviral treatment. The use of ART may also be challenging to individuals. The findings of this study were that not all participants in the study experienced challenges with taking ART. Those who experienced challenges included fear of disclosing HIV status, fear of stigmatization and physical challenges due to ill health. Regarding the reasons for defaulting ART, participants’ reasons for defaulting antiretroviral treatment were similar although some of the reasons applied to only one participant. Participants’ reasons for treatment default were classified into socio-economic factors, patient related, psychological related and medication related factors. Socio- economic factors included shortage of food in the household and lack of money for transport to attend clinic appointments. Patient related factors included substance abuse, lost appointment cards, participants were too busy with personal issues and relocation to another area of residence. Psychological factors that contributed to non-adherence to treatment were depression and denial. Medical related factor voiced was that participant was too confused about the drug regimen. Most participants were satisfied with the services in Thekganang ARV clinic although some participants raised concerns about staff attitudes and long queue. The findings will assist the hospital management and the clinic staff to make informed decisions about the management of defaulters in the clinic. The study was concluded with the relevant recommendations to the ART facilities. The recommendations included implementation of the multi-disciplinary centred approach, establishing patient education programmes and on-going support services to patients who fail to adhere to treatment. Future research studies should determine the prevalence of drug resistant HIV patients in the ART facilities and the development of a systematic method of capturing ‘‘lost to follow up’’ patients who pass away within hospitals. / Dissertation (MA)--University of Pretoria, 2014. / lk2014 / Social Work and Criminology / MA / Unrestricted

>Magister Scientiae - MSc / Background and Aims Human Immunodeficiency Virus (HIV) type 1 group M subtype C (HIV-1C) accounts for nearly half of global HIV-1 infections, with South Africa (SA) being one of the countries with the highest infection burden. In recent years, SA has made great strides in tackling its HIV epidemic, resulting in the country being recognized globally as the one sub-Saharan country with the largest combination antiretroviral therapy (cART) programme. Regardless of the potency of cART, the efficacy of the treatment is limited and hampered by the emergence of drug resistance. The majority of research on HIV-1 infections, effect of antiretroviral (ARV) drugs and understanding resistance to ARV drugs has been extensively conducted, but mainly on HIV-1 subtype B (HIV-1B), with less information known about HIV-1C. HIV-1’s viral Integrase (IN) enzyme has become a viable target for highly specific cART, due to its importance in the infection and replication cycle of the virus. The lack of a complete HIV-1C IN protein structure has negatively impacted the progress on structural studies of nucleoprotein reaction intermediates. The mechanism of HIV-1 viral DNA’s integration has been studied extensively at biochemical and cellular levels, but not at a molecular level. This study aims to use in silico methods that involve molecular modeling and molecular dynamic (MD) simulations to prioritize mutations that could affect HIV-1C IN binding to DNA and the IN strand-transfer inhibitor (INSTI) dolutegravir (DTG). The purpose is to help tailor more effective personalized treatment options for patients living with HIV in SA. This study will in part use patient derived sequence data to identify mutations and model them into the protein structure to understand their impact on the HIV-1C IN protein structure folding and dynamics. Methods Our sample cohort consisted of 11 sample sequences derived from SA HIV-1 treatmentexperienced patients who were being treated with the INSTI raltegravir (RAL). The sequences were submitted to the Stanford HIV resistance database (HIVdb) to screen for any new/novel variants resulting from possible RAL failure. Some of these new variants were analyzed to analyse their effect, if any, on the binding of DTG to the HIV-1C IN protein. Additionally, an HIV-1C IN consensus sequence constructed from SA’s HIV-1 infected population was used to model a complete three-dimensional wild type (WT) HIV-1C IN homology model. All samples were sequenced by our collaborators at the Division of Medical Virology, Stellenbosch University together with the National Health Laboratory Services (NHLS), SA. The HIV-1CZA WT-IN protein enzyme was predicted using SWISS-MODEL, and the quality of the resulting model validated. Various analyses were conducted in order to study and assess the effect of the selected new variants on the protein structure and binding of DTG to the IN protein. The mutation Cutoff Scanning Matrix (mCSM) program was used to predict protein stability after mutation, while PyMol helped to study any changes in polar contact activity before and after mutation. PyMol was also used to generate four mutant HIV-1C IN complex structures and these structures together with the WT IN were subjected to production MD simulations for 150 nanoseconds (ns). Trajectory analyses of the MD simulations were also conducted and reported. Results A total of 21 new variants were detected in our sample cohort, from which only six were chosen for further analyses within the study. A homology model of HIV-1C IN was successfully constructed and validated. The structural quality assessment indicated high reliability of the HIV-1C IN tetrameric structure, with more than 90.0% confidence in modelled regions. Of the six selected variants, only one (S119P) was calculated to be slightly stabilizing to the protein structure, with the other five found to be destabilizing to the IN protein structure. Variant S119P showed a loss in polar contacts that could destabilize the protein structure, while variant Y143R, resulted in the gain of polar contacts which could reduce flexibility of the 140’s region affecting drug binding. Similarly, mutant systems P3 (S119P, Y143R) and P4 (V150A, M154I) showed reduced hydrogen bond formation and the weakest non-bonded pairwise interaction energy. These two systems, P3 and P4, also showed significantly reduced to none polar contacts between DTG, magnesium (MG) ions and the IN protein, compared to the WT IN and P2 mutant IN systems. Interestingly, the WT structure and systems P1 (I113V) and P2 (L63I, V75M, Y143R) showed the highest non-bonded interaction energy, compared to systems P3 and P4. This was further supported by the polar interaction analyses of simulation clusters from the WT IN and mutant IN system P2 (L63I, V75M, Y143R), which were the only protein structures that formed polar contacts with DTG, MG ions and DDE motif residues, while P1 only made contacts with DNA and IN residues. Conclusion Findings from this study leads to a conclusion that double mutants (S119P, Y143R) and (V150A, M154I) may result in a reduction in the efficacy of DTG, especially when in combination. Furthermore, variants identified in systems P1 and P2 may still allow for effective DTG binding to IN and outcompete viral DNA for host DNA to prevent strand transfer. To the best of our knowledge, this is the first study that uses the consensus WT HIV1C IN sequence to build an accurate 3D homology model to understand the effect of less frequently detected/reported variants on DTG binding in a South African context. https://etd.

The human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) that subsequently develops remain major health concerns even after three decades since the first cases were reported. Successful therapeutic measures to address HIV/AIDS consist mostly of combinations of drugs targeting viral enzymes including reverse transcriptase (RT), protease (PR) and integrase (IN) as well as entry steps of the viral life cycle. The remarkable benefits (e.g. improved quality of life) derived from the use of these agents are unfortunately limited by toxicity to the host and the development of drug resistant viral strains. Drug resistance limits the repertoire of drug combinations available. Unfortunately, because latent forms of the virus exists, therapy has to be life-long and with new infections occurring every day, resistant strains tend to spread. To circumvent these problems, new drugs that inhibit resistant strains or work against new viral targets have to be developed. The history of gold compounds as potential inhibitors of HIV prompted this study in which twenty seven compounds consisting of gold(I), gold(III) and precursors from five classes were tested for drug-likeness, anti-HIV and immunomodulatory effects using wet lab and in silico methodologies. Cytotoxicity determination was done using viability dyes and flow cytometry. Cell proliferation profiles were monitored using the carboxyflourescein succinimidyl ester dye dilution technology and a real time cell analyser for confirming viability dye findings. The compounds’ effects on viral enzymes was determined using direct enzyme assays and in silico molecular modelling techniques. H and P nuclear magnetic resonance spectroscopy studies for determining stability revealed that the backbone chemical shifts of the compounds were relatively unchanged after one week (-20 and 37 ºC) when dissolved in dimethylsulfoxide. Eight of the gold compounds had drug-like properties comparable to clinically available drugs when in silico predictions were performed. The 50% cytotoxic dose of the compounds in human cells was between 1 and 20 μM (clinically relevant concentrations for gold compounds). Three gold(I) compounds inhibited viral infectivity at non-toxic concentrations and two gold(III) compounds did so at cytostatic (anti-proliferative mechanism that is also antiviral) concentrations. In the immunomodulatory assay, cytokine levels were altered by five compounds with one gold(I) and a gold(III) compound significantly reducing the frequency of CD4+ cells (an anti-viral function) from HIV+ donors (p= 0.005 and 0.027 respectively) when multi-parametric flow cytometry was performed. Inhibition of RT activity was predicted in in silico studies to be through interactions with the ribonuclease (RNase) H site although with poor stereochemical orientation while favourable binding predictions with the IN cofactor binding site were observed for some gold(III) complexes. Compounds predicted to interact with the RNase H site of RT and the IN cofactor site require structural modification to improve drug-likeness and binding affinity. The drug-like compound(s) which inhibited viral infectivity and lowered CD4+ cell frequency have potential for incorporation into virostatic cocktails (combination of cytostatic and directly anti-viral agent). Cytostatic agents are known to be less prone to drug resistance and because they lower CD4+ cell frequency, such compounds can potentially limit HIV immune activation. / Thesis (PhD)--University of Pretoria, 2011. / Biochemistry / unrestricted

The human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic has surpassed forty years with many medical advancements in prevention and treatment. Often believed to be at negligible or low risk by society at large, sexual minority women have remained understudied regarding their risk of HIV and other sexually transmitted infections (STIs), leaving their sexual health inadequately understood and supported in healthcare and social services. The sexual health of young South Asian sexual minority women, who are multiply minoritized due to their intersecting identities, has been entirely overlooked. This qualitative study aimed to understand the knowledge, attitudes, and practices of young South Asian sexual minority women as it pertains to their HIV/STI risk. Barriers and facilitators to accessing community-based sexual health supports and services were also investigated. A community-engaged approach was taken to develop this study in partnership with the Alliance for South Asian AIDS Prevention to investigate the HIV/STI risk context and sexual health needs of this group residing in the Greater Toronto Area. A maximum variation sampling strategy was used to recruit six young South Asian sexual minority women and semi-structured in-depth interviews were conducted to collect narrative data. Narrative analysis of the data found socio-cultural and structural influences which guide the HIV/STI risk context for this group. The participants illuminated an inadequate understanding of sexual health when engaging in sex with women, an overall low HIV/STI risk perception, barriers to adequate sexual healthcare and health promotion resources, and multiple minority stressors which impacted their access to safe sex. These findings have major implications for school-based sexual health education, medical training for healthcare practitioners, and sexual health support and services provided by community-based sexual health organizations in the Greater Toronto Area. / Thesis / Master of Public Health (MPH)

Magister Pharmaceuticae - MPharm / Background: Tenofovir disoproxil fumarate (TDF) and Zidovudine (AZT) are both nucleotide and nucleoside analogue reverse transcriptase inhibitors (NtRTIs and NRTIs), respectively. They are used for the management and prevention of the Human Immunodeficiency Virus (HIV) infection. These drugs are faced with oral delivery challenges such as low intestinal permeability and extensive first pass liver metabolism for TDF and AZT, respectively. Their use may also be limited by dose-dependent adverse effects, which may result in treatment failure when patients become non-compliant and non-adherent to their prescribed antiretroviral (ARV) regimen. Non-compliance and non-adherence to ARV regimen may lead to drug resistance and a need for change in regimen, which can be very expensive, not only financially but in terms of morbidity and mortality. To solve such issues, a new drug can be formulated, or an existing drug can be modified. The development and formulation of a new drug is time consuming and expensive, especially with no available data and a high probability of failure. Modifying existing drugs is a cheaper, less time-consuming option with lower probability of failure. Such modification can be achieved via non-covalent interactions using various methods such as preparation of nano-particulates with polymeric micelles (a non-covalent interaction). Polymeric micelles offer a variety of polymers to choose from for drug modification purposes. Purpose: The aim of this study was to formulate polymeric nanoparticles of TDF and AZT using different ratios of poly-lactic-co-glycolic acid (PLGA), characterize the formulated nanoparticles (using the following analyses: particle size, zeta potential, encapsulation efficiency, hot stage microscopy, thermogravimetric analysis, differential scanning calorimetry, Fourier transform infrared spectroscopy and scanning electron microscopy), analyze for stability during storage (2-8˚C) and determine the release rate of the active pharmaceutical ingredients in the formulated nanoparticles. Methods: Nanoparticles were prepared using a modified version of the double emulsion (water-in-oil-in-water) solvent evaporation and diffusion method. Two ratios of PLGA (50:50 and 85:15) were used to prepare four formulations (two each of TDF and AZT). Thereafter, the physicochemical and pharmaceutical properties of the formulations were assessed by characterizing the nanoparticles for particle size, zeta potential, polydispersity index, percentage yield, release profile and particle morphology, using the suggested analytical techniques. Results: For TDF-PLGA 85:15, TDF-PLGA 50:50, AZT-PLGA 85:15 and AZT-PLGA 50:50, nanoparticles of 160.4±1.7 nm,154.3±3.1 nm,127.0±2.32 nm and 153.2±4.3 nm, respectively, were recovered after washing. The polydispersity index (PDI) values were ≤0.418±0.004 after washing, indicating that the formulations were monodispersed. The zeta potential of the particles was -5.72±1 mV, -19.1 mV, -12.2±0.6 mV and -15.3±0.5 mV for TDF-PLGA 85:15, TDF-PLGA 50:50, AZT-PLGA 85:15 and AZT-PLGA 50:50 respectively after washing. The highest percentage yield was calculated to be 79.14% and the highest encapsulation efficiency obtained was 73.82% for AZT-PLGA 50:50, while the particle morphology showed spherical nanoparticles with signs of coalescence and aggregation for all formulated nanoparticles. The release profiles were biphasic; that is, an initial burst which indicated the presence of surface API followed by sustained release. Comparing the release profiles of AZT and TDF at pH 1.2 and 7.4, it was indicative that more AZT was released at pH 1.2 while more TDF was released at pH 7.4. On computing the release data further into various mathematical models, the Weibull model was found to be the best fit. The loaded nanoparticles showed an increase in stability after washing; however, they showed signs of gradual decrease in stability after 10 days of storage at 2-8°C. Conclusions: Relatively small, spherical and smooth nanoparticles were formulated. The nanoparticle release profile was indicative of sustained release; however, there was no conclusive indication that 48 hours duration was sufficient to release all encapsulated drug. Further studies with an increased API or polymer ratio in the formulation needs to be performed to determine if the encapsulation efficiency can be improved and in-vivo studies are required for a better understanding of the API release from formulations as well as its absorption in the body.