Thesis (Ph. D.)--Florida State University, 2003. / Advisor: Dr. David Sly, Florida State University, College of Social Sciences, Dept. of Sociology. Title and description from dissertation home page (viewed Oct. 7, 2003). Includes bibliographical references.

Thesis (Ph. D.)--University of Washington, 2003. / Vita. Includes bibliographical references (leaves 129-137).

Thesis (Ph. D.)--Ohio State University, 2003. / Title from first page of PDF file. Document formatted into pages; contains x, 141 p.; also includes graphics. Includes abstract and vita. Advisor: Thomas Gregoire, College of Social Work. Includes bibliographical references (p. 109-122).

Thesis (MSD (EAP))--University of Pretoria, 2003.

published_or_final_version / Public Health / Master / Master of Public Health

Asia has populated with the second largest number of people living with HIV/AIDS. Under the advancement of transportation, the open up of borders between cities and countries, and the process of globalisation, people move from their place of origin to other places for better living conditions and employment opportunities. Mobile people and migrants are identified as the high risk population of HIV infection. Poverty, discrimination, limited access to healthcare and social services, separation with supports and families, being alienated in resident communities, and gender inequalities are the unfavourable conditions which make the migrant population vulnerable to HIV infection. Existing literatures have investigated and examined the potential risk factors among the mobile population. Inconsistencies were found among research but high risk sexual behaviours and poor knowledge and attitude were observed and reviewed within the migrants. However, literatures which compared the people who migrated with other local people in the same population were not yet reviewed systemically. Therefore, this paper aimed to review the articles which compare the migrant group and the non-migrant group in Asian population to identify the association between migration and the risks of HIV infection. A literature search of five databases (PubMed, Medline, Cochrane, CNKI, Wanfang Med Online) was performed and nine articles were eventually selected for review. The migration status of literature was studied as explanatory variable and compared across studies. Outcome variables of interest were grouped into four categories as: demographic characteristics, sexual practices, awareness towards HIV/AIDS, and disease prevalence. To conclude, compared to people who did not migrate, migrants in Asia were more tend to be less educated, have multiple sex partners, engage in high risk sexual intercourse and commercial sex, but their overall condom usage were lower. Also, they had higher risk of sexually transmitted infections and poorer knowledge in HIV/AIDS. / published_or_final_version / Public Health / Master / Master of Public Health

Our research laboratory has recently reported that mucosal priming with a replicating modified vaccinia Tiantan virus (MVTTgpe)-based vaccine elicits durable protection against pathogenic SIVmac239 infection in rhesus monkeys. However, the protective role of vaccine-elicited antibody responses remains poorly understood. Here, a novel yeast surface displayed (YSD) antigen library was established to quantitatively map the antigenic determinants presented by MVTTgpe-based and control vaccines as well as by SIVmac239 infection. The YSD-library allows the mapping of linear and some conformational epitopes as a major technical innovation, as validated by testing SIV-specific mAbs KK65, KK8 and VM-18S. While eight antigenic domains are characterized covering the entire SIVmac239 gp160, the MVTTgpe/Ad5gpe regimen uniquely induces antibody responses against a distinct major antigenic determinant (MAD) in V2 region as compared with the Ad5gpe/Ad5gpe vaccination and SIV infection. This MAD is associated with a higher titer of anti-V2 antibody responses, which inversely correlates with peak viral load. Unexpectedly, the MVTTgpe/Ad5gpe vaccine- challenge. The results showed that instead of recalling B cell memory response to V2, viral infection presents a distinct set of antigenic determinants with anti-V1V2 antibodies primarily directed to V1 region. Moreover, the anti-V1V2 antibody responses disappear in two infected macaques after they enter the stage of simian AIDS. SIVmac239 infection, therefore, can modulate vaccine-elicited B cell immunity by diminishing anti-V2 antibody memory responses in rhesus monkeys. These findings implicated that vaccine efforts with focus on V2 region would require periodic vaccinations to maintain a long-lasting high level of antibody responses for protection. In the absence of an effective vaccine for eliciting HIV-1-specific broadly neutralizing antibodies (bNAbs), passive immunization with bNAbs or Ab-like agents (e.g. immunoadhesin) becomes an attractive alternative for HIV-1 prevention. In this study, we aimed to design, optimize and produce secretory immunoadhesins (IAs) based on gene engineering of existing HIV-1 specific bNAbs for potency and production improvements. IAs are chimeric, antibody-like molecules that combine the functional domain of bNAb with immunoglobulin constant domains, including the hinge and Fc regions. We found that the modified secretory IAs not only preserved the neutralization activity of the parental bNAbs, but also had enhanced expression and smaller molecular size that is suitable for antibody gene-based in vivo delivery. Furthermore, we defined the synergistic effects of five IAs against HIV-1 infection and subsequently engineered two types of bi-specific IAs by combining the functional domains of Hu5A8, a humanized anti-CD4 antibody, and the bNAb PGT128. Significantly, one of the bi-specific IA, namely Bi-IA-Mono, neutralized 100% of the 33 viruses tested, including the transmitted/founder viruses and viruses resistant to both parental IAs. The remarkably enhanced neutralization activity of Bi-IA-Mono, either in potency and breadth, indicated the great potential of modified bi-specific IA to provide complete or nearly complete protection against major HIV-1 subtypes. Overall, our results demonstrated that the engineering of IA and bi-specific IA is an attractive way to improve anti-HIV-1 properties of existing bNAbs, which have significant implications for antibody-based prophylactics in blocking diverse HIV-1 transmissions and infections. / published_or_final_version / Microbiology / Doctoral / Doctor of Philosophy

Acquired immunodeficiency syndrome (AIDS) is a major problem in our current society. There are over 35 million of the population that are currently living with human immunodeficiency virus (HIV), and the number of HIV-infected patients are still rising every year in spite of our efforts to control it. Furthermore, within the AIDS affected population, opportunistic infection is a major cause of complications and is the number one cause of death. The HIV trans-activator (Tat) protein plays a major role in the AIDS pathogenesis. HIV-1 Tat is known to cause dysregulation of cytokines such as TNF-α, IL-6, and IL-10 in AIDS patients. In this study we recognized a proto-oncogene, c-Myc, could regulate the cytokine dysregulation caused by HIV-1 Tat in primary blood monocyte derived macrophages (PBMac). By knocking down the expression of c-Myc with gene specific small-interfering RNA (siRNA), we demonstrated that c-Myc may be critical for the expression of the pro-inflammatory cytokines TNF-α and IL-6. HIV-1 Tat was subsequently found to regulate the expression of c-Myc via the activation of dsRNA-activated protein kinase (PKR), ERK1/2 and p38 mitogen-activated protein kinase (MAPK). Furthermore, c-Myc regulation of the pro-inflammatory cytokines was demonstrated to have a role in AIDS related opportunistic infections. HIV-1 Tat was shown to increase the intracellular growth of Mycobacteria avium complex (MAC) within PBMac. This increase in MAC growth was in turn found to be regulated by TNF-α expression controlled by c-Myc. HIV-1 Tat was also demonstrated to induce the expression of RIG-I, a common pattern recognition receptor of double stranded RNA viruses, in PBMac. RIG-I is known to activate the viral immune responses such as the type-I interferon (IFN) and pro-inflammatory cytokine pathways. This induction of RIG-I by HIV-1 Tat was found to be regulated by c-Myc, as well as through other signalling kinases such as p38 MAPK and PKR. Tat induction of RIG-I ultimately led to the induction of IFN-α2 and IFN-β through the expression and nuclear translocation of the interferon regulatory factor-7 (IRF-7). This alteration in type-I IFN expression regulated by HIV-1 Tat and RIG-I was also found to play a role against AIDS related opportunistic infections. HIV-1 Tat is known to increase the infectivity of Kaposi’s sarcoma-related herpesvirus (KSHV), a common opportunistic viral infection. We were able to demonstrate that this increase in KSHV infectivity was regulated by RIG-I and type-I IFN induced by HIV-1 Tat. Lastly, this study also demonstrated how HIV-1 Tat was able to manipulate the expression of IL-8 induced by KSHV in PBMac. HIV-1 Tat was able to mediate the production of IL-8 induced by KSHV by altering the phosphorylation of the p38 MAPK and the signal transducer and activator of transcription-1 (STAT-1). Taken together, the results of this study showed how c-Myc and RIG-I may be able to play critical roles in HIV-1 Tat induced cytokine dysregulation. Furthermore, the importance of these pathways is further demonstrated in their roles in regulating the immune responses against opportunistic infections in AIDS patients. / published_or_final_version / Paediatrics and Adolescent Medicine / Doctoral / Doctor of Philosophy

Thesis (DTech. in the Dept. of Drama and Film Studies.)--Tshwane University of Technology, 2012. / When theatre officially was acknowledged as an interventionist tool in the fight against HIV/AIDS in South Africa in 1996, economic and political evils of apartheid of the past. Unfortunately, as statistics have revealed, this has not been the case, as HIV prevalence levels have continued to rise in all sections of society. In trying to understand the reasons for theatre's failed attempts at changing peoples' sexual behaviour, scholars have identified the non-centrality of cultural norms of target audiences as one of the principal causes.it was hoped that it would effectively and efficiently deal with raising the awareness levels of the South African population of the dangers of HIV, and the consequences of risky sexual behaviour given its immense contribution in creating awareness about the social Health communication experts have agreed that health intervention strategies seem to be controlled by people who do not understand the complexity of the behaviour of their target audiences. Health behaviour theorists have also indicated the need to re-examine intervention approaches by paying more attention to the culture of the target population. This study therefore, investigated the inclusion/non-inclusion of cultural norms of target audiences in the design of theatre's dramatic performances which serves as its intervention instrument. This was done through an examination of three theatre groups' HIV/AIDS campaigns in three provinces of South Africa. Using qualitative study methods, the study probed into whether the cultural values of the communities concerned are encapsulated in the plays performed by the groups to spread awareness of HIV/AIDS.

Background. Numerous methods have been developed to model longitudinal data. In HIV/AIDS studies, HIV markers, CD4+ count and viral load are measured over time. Informative drop-out and the lower detection limit of viral load assays can bias the results and influence assumptions of the models. Objective The objective of this thesis is to describe the evolution of HIV markers in an HIV-1 subtype C acutely infected cohort of women from the CAPRISA 002: Acute Infection Study in Durban, South Africa. They were HIV treatment naive. Methods. Various linear mixed models were fitted to both CD4+ count and viral load, adjusting for repeated measurements, as well as including intercept and slope as random effects. The rate of change in each of the HIV markers was assessed using weeks post infection as both a linear effect and piecewise linear effects. Left-censoring of viral load was explored to account for missing data resulting from undetectable measurements falling below the lower detection limit of the assay. Informative drop- out was addressed by using a method of joint modelling in which a longitudinal and survival model were jointly linked using a latent Gaussian process. The progression of HIV markers were described and the effectiveness and usefulness of each modelling procedure was evaluated. Results. 62 women were followed for a median of 29 months post infection (IQR 20-39). Viral load increased sharply by 2.6 log copies/ml per week in the first 2 weeks of infection and decreased by 0.4 log copies/ml per week the next fortnight. It decreased at a slower rate thereafter. Similarly CD4+ count fell in the first 2 weeks by 4.4 square root cells/ul per week then recovered slightly only to decrease again. Left-censoring was unnecessary in this acute infection cohort as few viral load measures were below the detection limit and provided no improvement on model fit. Conclusion. Piecewise linear effects proved to be useful in quantifying the degree at which the HIV markers progress during the first few weeks of HIV infection, whereas modelling time as a linear effect was not very meaningful. Modelling HIV markers jointly with informative drop-out is shown to be necessary to account for the missing data incurred from participants leaving the study to initiate ARV treatment. In ignoring this drop-out, CD4+ count is estimated to be higher than what it actually is. / Thesis (M.Sc.)-University of KwaZulu-Natal, Pietermaritzburg, 2009.