A thesis submitted to the Faculty of Science University of the Witwatersrand Johannesburg in fulfillment for the requirements of the degree of Master of Science. 14 May 2015. / Peptidomimetic compounds have been shown to exhibit both anti-HIV and anti-malarial activity. A multicomponent reaction was used to create a library of peptidomimetic compounds with an α-hydroxy-β-amino acid unit. The Passerini reaction between an aldehyde, carboxylic acid and isocyanide was used to prepare compounds containing both ester and amide functionalities. These compounds were then subjected to a deprotection-acyl migration strategy giving rise to the target compounds. This approach, known as the Passerini Amine Deprotection Acyl Migration (PADAM) sequence was successfully used to create a library of novel peptidomimetic compounds. From this library, 22 compounds were tested for activity against HIV and malaria. The Passerini reaction gives rise to a product containing a new stereogenic centre, and as the starting aldehyde used (N-Boc-phenylalaninal) has a stereogenic centre, the products were isolated as a mixture of diastereomers. Our research was also focused on finding ways of influencing the stereoselectivity of the reaction and the separation of the resulting diastereomers. The diastereomeric ratio of the Passerini products was found to be approximately 2:1 for all the reactions performed. This ratio could be modified slightly when using certain carboxylic acids and isocyanides that were either very bulky or had a stereogenic centre. Attempts to enzymatically resolve the diastereomeric products were not successful after trials using a library of 25 lipase enzymes. However, use of preparative HPLC enabled the successful separation of most of the diastereomeric mixtures, affording compounds with high purity. X-ray crystallography enabled us to identify the major diastereomers as having the R,S configuration, whilst the minor diastereomers had the S,S configuration at the two stereogenic centres. A possible explanation for the observed stereoselectivity is based on the Felkin-Anh chelation control model. It suggests that mono-protected amino aldehydes follow a chelation controlled mechanism in nucleophilic addition reactions. Chelation occurs, albeit in the form of hydrogen bonding, between the NH and carbonyl oxygen. The library of compounds was tested for activity against both HIV-1 and malaria. Only three compounds showed moderate activity against the malaria parasite, inhibiting parasitic growth by 37-42% at 5 μM respectively. Significantly, all of the active compounds contained an adamantyl moiety. Unfortunately no anti-HIV activity was seen for any of the compounds tested in the HIV-assay.

Li, Sai Kam. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 177-200). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Analysis of integrated, diverse, Human Immunodeficiency Virus (HIV)-associated datasets can increase knowledge and guide the development of novel and effective interventions for disease prevention and treatment by increasing breadth of variables and statistical power, particularly for sub-group analyses. This topic has been identified as a National Institutes of Health research priority, but few efforts have been made to integrate data across HIV studies. Our aims were to: 1) Characterize the semantic heterogeneity (SH) in the HIV research domain; 2) Identify HIV-associated common data elements (CDEs) in empirically generated and knowledge-based resources; 3) Create a formal representation of HIV-associated CDEs in the form of an HIV-associated Entities in Research Ontology (HERO); 4) Assess the feasibility of using HERO to semantically harmonize HIV research data. Our approach was guided by information/knowledge theory and the DIKW (Data Information Knowledge Wisdom) hierarchical model. Our systematized review of the literature revealed that synergistic use of both ontologies and CDEs included integration, interoperability, data exchange, and data standardization. Moreover, methods and tools included use of experts for CDE identification, the Unified Medical Language System, natural language processing, Extensible Markup Language, Health Level 7, and ontology development tools (e.g., Protégé). Additionally, evaluation methods included expert assessment, quantification of mapping tasks between raters, assessment of interrater reliability, and comparison to established standards. We used these findings to inform our process for achieving the study aims. For Aim 1, we analyzed eight disparate HIV-associated data dictionaries and developed a String Metric-assisted Assessment of Semantic Heterogeneity (SMASH) method, which aided identification of 127 (13%) homogeneous data element (DE) pairs and 1,048 (87%) semantically heterogeneous DE pairs. Most heterogeneous pairs (97%) were semantically-equivalent/syntactically-different, allowing us to determine that SH in the HIV research domain was high. To achieve Aim 2, we used Clinicaltrials.gov, Google Search, and text mining in R to identify HIV-associated CDEs in HIV journal articles, HIV-associated datasets, AIDSinfo HIV/AIDS Glossary, AIDSinfo Drug Database, Logical Observation Identifiers Names and Codes (LOINC), Systematized Nomenclature of Medicine (SNOMED), and RxNORM (understood as prescription normalization). Two HIV experts then manually reviewed DEs from the journal articles and data dictionaries to confirm DE commonality and resolved semantic discrepancies through discussion. Ultimately, we identified 2,179 unique CDEs. Of all CDEs, data-driven approaches identified 2,055 (94%) (999 from the HIV/AIDS Glossary, 398 from the Drug Database, 91 from journal articles, and a total of 567 from LOINC, SNOMED, and RxNorm cumulatively). Expert-based approaches identified 124 (6%) unique CDEs from data dictionaries and confirmed the 91 CDEs from journal articles. In Aim 3, we used the Protégé suite of ontology development tools and the 2,179 CDEs to develop the HERO. We modeled the ontology using the semantic structure of the Medical Entities Dictionary, available hierarchical information from the CDE knowledge resources, and expert knowledge. The ontology fulfilled most relevant criteria from Cimino’s desiderata and OntoClean ontology engineering principles, and it successfully answered eight competency questions. Finally, for Aim 4, we assessed the feasibility of using HERO to semantically harmonize and integrate the data dictionaries from two diverse HIV-associated datasets. Two HIV experts involved in the development of HERO independently assessed each data dictionary. Of the 367 DEs in data dictionary 1 (D1), 181 (49.32%) were identified as CDEs and 186 (50.68%) were not CDEs, and of the 72 DEs in data dictionary 2 (D2), 37 (51.39%) were CDEs and 35 (48.61%) were not CDEs. The HIV experts then traversed HERO’s hierarchy to map CDEs from D1 and D2 to CDEs in HERO. Of the 181 CDEs in D1, 156 (86.19%) were found in HERO, and 25 (13.81%) were not. Similarly, of the 37 CDEs in D2 32 (86.48%) were found in HERO, and 5 (13.51%) were not. Interrater reliability for CDE identification as measured by Cohen’s Kappa was 0.900 for D1 and 0.892 for D2. Cohen’s Kappas for CDEs in D1 and D2 that were also identified in HERO were 0.885 and 0.688, respectively. Subsequently, to demonstrate the integration of the two HIV-associated datasets, a sample of semantically harmonized CDEs in both datasets was categorically selected (e.g. administrative, demographic, and behavioral), and D2 sample size increases were calculated for race (e.g., White, African American/Black, Asian/Pacific Islander, Native American/Indian, and Hispanic/Latino) and for “intravenous drug use” from the integrated datasets. The average increase of D2 CDEs for six selected CDEs was 1,928%. Despite the limitation of HERO developers also serving as evaluators, the contributions of the study to the fields of informatics and HIV research were substantial. Confirmatory contributions include: identification of effective CDE/ontology tools, and use of data-driven and expert-based methods. Novel contributions include: development of SMASH and HERO; and new contributions include documenting that SH is high in HIV-associated datasets, identifying 2,179 HIV-associated CDEs, creating two additional classifications of SH, and showing that using HERO for semantic harmonization of HIV-associated data dictionaries is feasible. Our future work will build upon this research by expanding the numbers and types of datasets, refining our methods and tools, and conducting an external evaluation.

Nearly 37 million people are living with HIV and there are an estimated 2.1 million new HIV infections each year, equating to 5,700 new infections per day. Approximately half of new HIV infections occur in Eastern and Southern Africa. Young people are at particularly high risk of HIV; 35% of new infections are among young people ages 15-24 years. In sub-Saharan Africa, 25% of new infections are among young women. Throughout the course of the HIV epidemic, research has described the associations between social structural and behavioral determinants of HIV acquisition. The influences of socioeconomic status, household characteristics, gender, geographical residence, and risky sexual behaviors on HIV acquisition are well reviewed in the literature. Evidence on the impact of education on factors that influence HIV acquisition is less robust and associations have changed over time as both education and the HIV epidemic have evolved. Globally, access to education and educational attainment has increased over the past several decades. In developing countries, the number of years enrolled in school for both men and women has significantly increased. The impact of increased educational attainment has contributed to reductions in child mortality, improvements in reproductive health, and reduced HIV transmission. In many countries, the gap in education between men and women has reversed, with women now achieving higher levels of educational attainment than men. However, in several low and middle income countries, gender disparities persist. Global public health, development, and policy communities recognize the importance of education and its influence on health outcomes. Over the past decade, education has been highlighted in the Millennium Development Goals (MDG) and now is continuing as a priority for the Sustainable Development Goals (SDG) in the post 2015-agenda. The goal of MDG 2 was to achieve universal primary education for all children; building on this goal, SDG 4 focuses on quality education, ensuring inclusive and equitable education and promoting lifelong learning opportunities for all. The goal of this dissertation is to highlight the importance of education by summarizing the current state of literature that reviews associations between education and HIV infection for adolescents in low- and middle- income countries and illuminating the key entry points for research, policy, and programming by examining the relationship of education on determinants of HIV infection for young people. This dissertation accomplishes the stated goal by: (1) Systematically reviewing associations between education and HIV infection for youth ages 13 – 24 years living in low- and middle- income countries (Chapter 1); (2) Examining the relationship between educational attainment on HIV acquisition for young adults ages 20 – 24 years in Rakai, Uganda (Chapter 2); and (3) Commenting on the pathways to HIV acquisition and identifying key entry points and best practices in policy and research to promote improved health outcomes for adolescents (Chapter 3). This dissertation is guided by both the proximate determinants of health framework as described in Chapter 2 and the socio-ecological theory adapted from the Bronfenbrenner Model as presented in Chapter 3. This dissertation adds to both the field of HIV and education research by synthesizing the literature that currently exists, illustrating the influence of education on known determinants of HIV acquisition, and concluding with actionable research and policy recommendations to continue progress toward educational attainment and improving health outcomes. A systematic review summarizes publications that analyze the association between education and HIV for young people living in low- and middle- income countries. Twenty-two articles include over 315,000 participants from 18 countries. While over half of the articles included in this review indicate that higher education is associated with lower rates of HIV sero-positivity, there is still significant variability in the findings. Two studies indicate that those with higher education have an increased risk of HIV; four studies show no association between education and HIV; and five studies result in mixed conclusions based on gender and age or grade level. Key conclusions from this review echo previous systematic reviews. Dates of data collection influence the conclusion of published studies. In this review, articles that show that those with more education had a lower HIV prevalence were more likely to have data collected after the year 2000. Although articles from 2007 – 2017 are eligible to be included in this review, the most recent publications identified are from 2015 and the most recent data are from 2013. More updated data collection and publications on the association between education and HIV are needed to continue to improve this field of study. This review highlights the importance of continuing research on the association between education and HIV in low- and middle- income countries to support continued progress toward MDG 2 and SDG 4. Not only is it imperative to study the relationship and magnitude of the association in a variety of settings and populations, but also to gain a better understanding of how and why education influences HIV for young people. This review provides sufficient evidence to show that education does have an impact on HIV and can be used to improve policies and programs to improve school enrollment, attendance, attainment, and the quality of education in low- and middle- income countries for all young people. In Uganda, school enrollment rose steadily from 1994 to 2013 among adolescents, due largely in part to changes in national policy. Increasing school enrollment in Uganda was associated with a declining risk for HIV and pregnancy among young people ages 15 – 19 years. Data from the Rakai Community Cohort Study (RCCS) were used to examine the association between educational attainment and proximate risk factors of HIV infection for young adults’ ages 20 – 24 years. Results showed that educational attainment was protective against several risk factors for HIV. Compared to those with no education, females with at least a secondary education were less likely to have their first sexual encounter before the age of 18. Compared to those with no education, females with higher educational attainment (attending primary school, secondary school, or beyond secondary school) were more likely to use family planning methods and had fewer sexual partners. Educational attainment was also correlated with riskier behaviors. Females with higher education were more likely to report inconsistent condom use, concurrent sexual partners, and were less likely to know the HIV status of their partners. Similar results were seen in males. Compared to those with no education, males with any education were more likely to use family planning methods. Compared to those with no education, males with higher education (attending primary school, secondary school, or beyond secondary school) were more likely to report concurrent sexual partners. Educational attainment was not significantly associated with HIV incidence in males or females. The association between educational attainment and risk factors for HIV acquisition are varied. Higher educational attainment is associated with delayed initiation of sexual activity and use of family planning methods; however, it is also associated with inconsistent condom use and more concurrent sexual partners. In an era of enhanced focus on education and educational attainment, this data helps explain how schooling can impact the risk behaviors that influence the HIV epidemic in young people. When developing sexual education in the future, researchers, program, and policy developers should utilize these findings to ensure curricula focus on consistent condom use, concurrent partners, and the importance of HIV disclosure. This study also highlights gaps in the current literature – future research questions should more closely examine the quality and content of education, as well as determining the role that education plays in exerting autonomy over behavior and behavior change. The HIV/AIDS epidemic and access to education have seen parallel improvements in recent decades. Nearly 40 years into the HIV/AIDS epidemic, there have been tremendous gains in care, treatment, and prevention of HIV. Yet, the epidemic still impacts millions of people worldwide. Similarly, access to education has improved for many throughout the twentieth and twenty-first centuries, although major disparities and gaps remain. The importance of education for health and development is highlighted by the United Nations (UN) in the Millennium Development Goal campaign (MDG, 2000 – 2015) and in the Sustainable Development Goals effort (SDG, 2015 – 2030)21,22. The UN calls for universal primary education (MDG 2) and inclusive and quality education for all (SDG 4)21,22. In the current post-2015 agenda focusing on eliminating disparities and improving quality in education, now is a pivotal time to review what is known and what remains to be discovered about the relationship between educational attainment and the HIV/AIDS epidemic, two driving domains in policy and program planning. More updated data and research needs to be conducted in a variety of diverse settings in order to understand how education can influence the HIV epidemic in the current environment. Moreover, researchers should ensure that they are looking at the entire context of education and desegregating educational attainment from socioeconomic status measured using alternative measures to better target key entry points for change. Policy makers can utilize this research to evaluate existing policies and implement new polices as needed. The failure to meet the MDG 2 of universal primary education indicates that much work still remains in the policy and program implementation realms of education enrollment and attainment. Beyond primary education, a renewed focus on secondary education, quality education, and gender equality will maximize the benefits of education.

Thesis (M.Sc.)--Memorial University of Newfoundland, 2005. / Includes bibliographical references.

Thesis (Ph. D.)--School of Public Policy, Georgia Institute of Technology, 2004. Directed by Paul G. Farnham. / Includes bibliographical references (leaf 127).

Source: Dissertation Abstracts International, Volume: 68-11, Section: B, page: 7281. Adviser: Lu-Yu Hwang. Includes bibliographical references.

Over the 30 years since it was first identified, the HIV/AIDS epidemic has had historically unprecedented severity and impact. There are approximately 33.4 million people living with HIV-1/AIDS which urges to seek novel approaches for HIV-1 diagnosis and HIV-1 therapy. Men who have sex with men (MSM) are severely affected by HIV-1 and constitute a large proportion of HIV-infected individuals. In Hong Kong, the transmission route of homosexual and bisexual contacts accounted for nearly 50% of incidence in 2012. To investigate HIV-1 prevalence among MSM in Hong Kong, the combination of fast antibody test (FAT) and real-time dried-blood-spot-based quantitative polymerase chain reaction (DBS-qPCR) was employed for 474 participants chosen randomly from community testing sites of MSM within a one-year period which showed a 4.01% (19/474) rate of HIV-1 prevalence among MSM in Hong Kong with three cases at the acute phase among the newly infected participants. The new survey demonstrated that the risk factors of MSM are mostly correlated with the receptive role during anal sex and syphilis infection. In this study, two traditional Chinese herbal medicines (TCHM), Sanguisorba officinalis (SO) and Spatholobus suberectus (SS), inhibited the infection of model cell lines expressing HIV-1 targets by HIV-1 pseudoviruses, while the anti-HIV-1 properties of SO were demonstrated for the first time. Both SO and SS were able to block not only infection by pseudoviral HIV-1 CCR5-tropic and CXCR4-tropic strains, but also RT and PI drug-resistant strains. Mechanistic studies revealed that SO and SS interact with the viral envelope to prevent the infection of target cells by HIV-1. Two compounds derived from SO and SS, named Gallic acid (GA) and Jiazhi (JZ), retained anti-HIV-1 properties and blocked HIV-1 infection by acting on the viral envelope. Small molecules derived from TCHM were also investigated for their capacity to activate HIV-1 from latency. A small molecule derived from SS, Daidzein (DDZ), demonstrated the potentials to trigger HIV-1 reactivation in latently infected cell lines. DDZ enhanced gene expression from HIV-1 LTR in which the Sp1 binding site plays an important role. The Akt pathway is also involved in the initiation of DDZ-induced activation. Phosflow analysis revealed that DDZ activated the Akt pathway in various subpopulations of T cells, including memory CD4+ T cells which are considered to be a major reservoir for HIV-1. The structure-activity relationships (SARs) study demonstrated the 4'-hydroxyisoflavone as bio-functional core structure. Addition of a hydroxyl group on C-5 position significantly decreases its biological function of HIV-1 latency activation. In summary, this study investigates HIV prevalence and incidence using an assay for early HIV-1 diagnosis and performs an analysis of risk factors of behavior which contributes to the effective control of HIV transmission in Hong Kong and its neighbors in Asia. It also demonstrates a drug research sourced from traditional Chinese herbal medicines that which sheds lights on drug discovery from traditional herbal medicines and facilitates mechanistic drug design for HIV-1 eradication. / published_or_final_version / Microbiology / Doctoral / Doctor of Philosophy

To date, the HIV/AIDS pandemic remains a global disaster. The sheer scale of the pandemic and the limited success of prevention programmes in controlling its spread have necessitated an urgent need for the development of a safe, effective and affordable HIV preventive vaccine. However, perceptions of HIV vaccines and the relationships between HIV/AIDS knowledge, perceived risk and existing views on HIV vaccines are minimum characteristics required to make future HIV vaccines a worthwhile public health tool. This study reports findings among representatives of the ethnic groups aged between 18 and 49 in the Rustenburg community of Bojanala district (N = 351). The study utilized some of the data collected by the Aurum Institute of Health Research representative household survey that forms part of a range of HIV vaccine preparedness studies in the Bojanala area, Rustenburg. Descriptive statistics were applied to all items. Independent samples T- tests and Analysis of variances (ANOVAs) were used to compare means. Correlational statistics (Pearson‘s product moment) was used to explore relationships between pairs of variables. A standard multiple regression analyses was applied to assess and explore the factor(s) that predict the likelihood that respondents would report supportive perceptions for HIV vaccines while the hierarchical model fitted was done to control for the influence of demographic variables. About 74% of the study participants had good knowledge of HIV/AIDS-related issues and the same percentage of respondents identified self and their community to be at risk of HIV/AIDS infection (measured as fatalism regarding risk of contracting HIV infection). Positive view-points regarding participation in vaccine trials and belief in a future HIV vaccine to protect from contracting HIV infection was reported by almost 90% of the study participants. Meanwhile, a majority (60%) had low levels of knowledge on HIV vaccines. The results of standard and hierarchical multiple regressions showed that knowledge on HIV/AIDS transmission, prevention and treatment (in particular) are the best predictors of perceptions of an HIV vaccine. Furthermore, with the exception of the duo of perceived HIV risk and perceptions of HIV vaccine, positive correlations were found among knowledge, perceived HIV risk and vaccine perceptions, as well as among these and exposure to the media. Race (being Black in particular) and low levels of education seem to be profound challenges facing HIV/AIDS related issues, particularly perceived HIV risk. The findings from this study have implications for strategies in HIV prevention, viz. education, service delivery, advocacy and policy among others at institutional, national, regional, and global level in both public and private sectors. Political will, unprecedented collaborative effort among stakeholders and review of the existing Expanded Programme of Immunization schedule are all required to make the future HIV vaccine globally available. In addition, deductions highlight several key areas where research is urgently needed. / Thesis (M.A.)-University of KwaZulu-Natal, Durban, 2010.

The intervention of Voluntary Counselling and Testing (VCT) for the Human Immunodeficiency Virus (HIV) is rapidly gaining ground as an essential component in the health care system in an effort to combat and confront the spread of this disease. In South Africa where this intervention is gradually being introduced the application of VCT and the benefits and consequences likely to ensue from the application of the procedure were evaluated in-depth using a grounded theory and quantitative approach to describe the psychosocial dynamics. The interactive transfer of information embodied in VCT forms an integral part of the intervention and will continue to do so even when antiretroviral dnugs are uniformly available throughout the South African healthcare service. The way in which the women who will undergo this procedure internalise and respond to the information imparted to them during the counselling is highly significant from an educational and empowering perspective, regardless of the outcome of the test result. The aim of the counselling is primarily to promote a rising consciousness amongst patients and subsequently within their communities in an endeavour to move away from what is termed 'exceptionalism' and towards 'normalisation' of the treatment of HIV/AIDS. Communicating the facts about HIV will help to dispel the myths and stigma which still surround the disease. A convenience sample of one hundred and twelve women were interviewed whilst attending antenatal clinics at four different sites in KwaZulu-Natal. In addition a small cross-sectional sample of service providers and key informants in communities situated near to the chosen sites were interviewed to explore the perceptions of VCT and HIV in the current health service and community environment. The findings revealed that there is to date no mandatory policy which offers VCT routinely at any of the health centres primarily due to the cost of testing, lack of posts for trained counsellors and timeous laboratory facilities. Confusion amongst health personnel regarding current policies of treatment regimens for HIV/AIDS patients, as well as differing opinions about feeding options for infants, can undermine counsellors' confidence to handle complex issues competently from an informed position. Recommendations are that trained counsellor posts with opportunities for updating of current policies, easily accessible laboratory facilities and suitable space for confidential counselling (both oral and visual) be implemented as a priority in the health service. A more comprehensive service should be universally implemented, not just in antenatal and communicable disease clinics for ethical reasons of equity between all members of society. In the same vein the networking and cumulative energy of NGOs, religious groups and health professionals must be harnessed to work synergistically to provide sustainable solutions for those living with HIV and those at risk of becoming infected. / Thesis (M.A.)-University of Natal, Durban, 2001.