90% of Human Immunodeficiency Virus (HIV) infections are acquired across the genital or gastrointestinal mucosa, and infection leads to profound depletion of CD4+ lymphocytes. Antiretroviral therapy can restore blood CD4+ T cells. However, immune dysfunction and defects in mucosal antimicrobial defence persist. Some CD4+ T-subsets, particularly antimicrobial Th17 cells, show enhanced susceptibility to HIV infection and are also preferentially depleted in the course of HIV infection; the latter may allow microbial translocation into the bloodstream. Genital infections have been shown to have direct mucosal immune effects and to increase susceptibility to HIV; however, the effect of systemic infections, such as Malaria (which is holo-endemic in some HIV prevalent regions) is unknown. Understanding the relationship between HIV, highly susceptible immune cells, immune activation and malaria infection on mucosal tissues has been the main focus of my thesis. In HIV-infected individuals, I explored whether HIV antiretroviral therapy restores gut Th17 populations and improves gut antimicrobial defences. Therapy restored gut Th17 populations in some, but not all individuals, but antimicrobial defence remained impaired. I then piloted a novel mucosal-optimized PCR assay to measure cervical immune gene responses, as standard mucosal assays are inadequate. I succeeded in measuring mitogen-induced, but not HIV-specific, cervical immune responses in HIV-infected individuals. Next, using this PCR platform I examined mitogen-induced cervical immune responses in individuals demonstrating reduced susceptibility to HIV, and found that they had reduced production of both Th17-associated and pro-inflammatory cytokines from cervical cells. Finally, in a murine model I found that malaria caused genital and gastrointestinal mucosal immune activation, and increased both the expression of mucosal HIV susceptibility immune markers, and mucosal T cell immune activation. In summary, insufficient gastrointestinal Th17 cells restoration does not underlie persistent mucosal immune activation and microbial translocation in HIV-infected people on therapy. A reduced frequency of highly susceptible Th17 cells in the cervix of HIV-exposed but uninfected individuals was identified as a correlate of reduced HIV susceptibility. Malaria, a common systemic infection in HIV-endemic countries, may enhance susceptibility to HIV through increasing putative immune markers of HIV susceptibility and immune activation in potential mucosal sites of HIV exposure.

Mode of access: World Wide Web. / Thesis (Ph. D.)--University of Hawaii at Manoa, 2005. / Includes bibliographical references (leaves 158-166). / Electronic reproduction. / Also available by subscription via World Wide Web / xiii, 166 leaves, bound col. ill. 29 cm. +

Thesis (M.S.)--University of Hawaii at Manoa, 2007. / Includes bibliographical references (leaves 57-63). / xii, 63 leaves, bound col. ill. 29 cm

The term, risk-taking, has often been used to describe some of the behaviours and their associated negative outcomes occurring during adloscence. Statistics have shown that South Africa has one of the highest rates of HIV/AIDS infection in the world, with most infections occurring during adolescence. The central aim in this study was to explore the relationship between current constructions of masculinity and risk-taking behaviours among a group of young South African men. It was an exploratory study, focused on exploring how young men construct their masculinities, and how this intersects with or impacts on adolescent male risk-taking behaviours. A key conclusion drawn at the end of this project was that some traditional notions of manhood still held sway, and these tied in strongly with how these participants constructed their masculinity.

South Africa is estimated to have one of the highest epidemics of HIV infection. Recent youth studies have found that youth aged 15-24 years are increasingly becoming vulnerable to HIV. Condom use is promoted as one of the key HIV prevention methods in South Africa. Face-to-face structured questionnaire interviews were conducted with a volunteer sample of rural active women and men aged 15-26 years living in 70 villages in the Eastern Cape Province. Most of the participants were recruited in schools.

<p>The Human Immune Virus (HIV) and Acquired Immuno Deficiency Syndrome (AIDS) isa pandemic that has worsened the plight of vulnerable communities and environments in Africa. It is estimated that 40,3 million adults and children are living with HIV and AIDS and 3.1 million adults and children died in 2004 in the world. Southern Africa is the most affected region with a very high HIV/AIDS prevalence rate. The primary objective of the proposed study was to examine livelihoods and coping strategies of HIV/AIDS-affected households of Zaka District in Zimbabwe. Attention was given to institutional frameworks for HIV/AIDS interventions as district and village level. A second objective of the study is whether interventions are appropriately aligned and responsive to household livelihoods and coping</p>

Background: A third of HIV-infected patients are co-infected with HCV in the developed world, and more of co-infected patients than ever before are dying because of liver related diseases today. Drug-related hepatotoxicity is a growing concern among human immunodeficiency virus (HIV) / hepatitis C virus (HCV) co-infected population. Nucleotide analogues containing HIV antiretroviral therapy, namely highly active anti-retroviral therapy (HAART), can induce mitochondrial toxicity. However, little is known about the effect of nucleotide analogues on the liver at the cellular and molecular level, and how it may affect treatment. Objective: To investigate whether liver tissue from HIV/HCV co-infected individuals will show greater liver mitochondrial toxicity if currently receiving antiviral HIV medication, compared to those who are not taking it. Methods: Liver biopsies were collected from 23 HIV/HCV co-infected males. Fourteen patients were on stable HAART (ON-HAART) and 9 were OFF-HAART, including 4 who stopped HAART >6 months prior and 5 who were HAART-nave. Liver mitochondrial toxicity was assessed by transmission electron microscopy-based quantitative stereological analyses of hepatocyte and mitochondrial morphometry, as well as by mitochondrial DNA (mtDNA) and mtRNA (COX1/(ß-actin) real-time-PCR quantification. Results: Hepatocytes tended to be larger in the ON-HAART group than in the OFF-HAART group (p=0.05), but they both showed similar mitochondrial volume fraction of the cell and mitochondrial crista density. Liver mtDNA and mtRNA levels were not significantly differentbetween ON-HAART and OFF-HAART. Hepatocyte lipid accumulation was significantly higher in HCV genotype 3 compared to genotype 1 infection ()=0.002), but was not associated with HAART status. Conclusions: We found no evidence or trend of increased mitochondrial toxicity in HIV/HCV co-infected individuals currently on HAART compared to those who are not. This finding could be relevant to the decision-making process with respect to initiating HCV therapy in this population.

Title page, contents and abstract only. The complete thesis in print form is available from the University of Adelaide Library. / This thesis focuses on behavioural interventions for preventing sexual transmission of HIV. The international literature on the evaluation of this type of intervention largely originates from developed countries and from Africa. China, where the AIDS epidemic is growing rapidly, lacks rigorous evaluation studies to determine the effectiveness of HIV prevention activities. This study develops a model to inform decision-making based on evidence generated in settings other than those for which policy is being developed. This model is illustrated through two case studies in China, the first on HIV/AIDS prevention strategies targeting young people, and the second on men who have sex with men. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1284184 / Thesis (Ph.D.) -- University of Adelaide, School of Population Health and Clinical Practice, 2007

This thesis assesses factors associated with a number of short and long-term outcomes in HIV-infected patients receiving antiretroviral treatment in Asia. Analyses in this thesis were based on two cohorts of HIV-infected patients; The Treat Asia HIV Observational Database (TAHOD), a multi-centre prospective observational cohort from countries in Asia-Pacific region, and the HIV Netherlands Australia Thailand (HIV-NAT) collaboration cohort, a cohort of patients treated with antiretroviral treatments at HIV-NAT in Bangkok, Thailand. We examined factors associated with time to immunological failure endpoints, such as CD4≤ 200 cells/??L, CD4≤ 100 cells/ ??L, and CD4 return to baseline, and with the virological failure endpoint, detectable viral load defined as a value greater than 500 copies/mL. Multivariate Cox proportional hazard models were used. Results showed that CD4 count at baseline and changes in CD4 strongly predicted immunological failure. For virological failure, detectable viral load at baseline was the strongest predictor. As a step to developing simplified monitoring strategies, in which patients with a low risk of failure could have their monitoring CD4 count and viral load tests deferred, we developed predictive models for each immunological and virological failure endpoint. Models were developed on the HIV-NAT cohort, and validated on the independent TAHOD cohort. For predictive models, the complementary log-log transformation for each endpoint was fitted appropriate to the interval censored nature of the data. To assess goodness-of-fit, cut-offs were defined for the predicted risks that separated patients from low risk to high risk. Overall, the observed versus expected failures from HIV-NAT data agreed quite well across all endpoints, probably reflecting that the HIV-NAT database was the data we built the models upon. Not only did these models fit the HIV-NAT database well, they also discriminated patients from low to high risk groups. When we validated models with TAHOD data, the observed and expected failures agreed well only in the model for CD4 count return to baseline. For most of the endpoints, the predictive models overestimated the number of failures, with predicted values larger than observed. However, the proportions of failures were lowest in the low risk group and highest in the high risk group, indicating that our models did discriminate between patients at high and low risk, and that the predictive models might still be of use for the purpose of simplified monitoring strategies. With CD4 count and viral load monitoring tests now comprising a large component of the cost of HIV treatment in resource limited settings, we developed and assessed a simplified monitoring strategy that aimed to reduce the numbers of monitoring tests performed. The predictive models developed earlier were used to calculate the probabilities of failure in TAHOD patients. We assumed that patients would have their CD4 and viral load assessments annually, at baseline and at one year, predicted risk of failure at ensuing clinical visits, week 12, 24 and 36. For patients at low predicted risk of failure at ensuing clinical visits, we assessed the effect of deferring monitoring tests, both in terms of blood tests avoided, and in terms of delaying detection of failure in some patients. A number of levels for the predicted risk of failure that lead to deferral of testing were evaluated. The results suggested that predicted probabilities of failure of 10% - 20% gave the best results across all failure endpoints. These cut-offs could save a median of 598 (51.6%) (range 37 (2.6%)_-1,218 (81.9%) ) blood tests over the first year of treatment, but would fail to detect 29 (18%) (range 10 (7.4%) - 128 (39.3%) ) failures. The median time from failure to detection in those patients who did fail and had deferred monitoring tests was 28 weeks. Rates of antiretroviral treatment change in TAHOD were examined. We identified patterns and factors associated with the rate of treatment change. Median time to the first treatment change was 3.2 years. Factors predicting rate of treatment change in TAHOD were treatment combination, being on second or third combination, number of drugs available in each site and being an injecting drug user. The overall rate of treatment change in TAHOD was 29 per 1OO-person-year. Around 30% of patients stopped their treatment due to adverse events. These rates of treatment change are lower than have been seen in patients in western countries. This may be due to patients in developing countries having access to fewer antiretroviral drugs than patients in developed countries.

Title page, contents and abstract only. The complete thesis in print form is available from the University of Adelaide Library. / This thesis focuses on behavioural interventions for preventing sexual transmission of HIV. The international literature on the evaluation of this type of intervention largely originates from developed countries and from Africa. China, where the AIDS epidemic is growing rapidly, lacks rigorous evaluation studies to determine the effectiveness of HIV prevention activities. This study develops a model to inform decision-making based on evidence generated in settings other than those for which policy is being developed. This model is illustrated through two case studies in China, the first on HIV/AIDS prevention strategies targeting young people, and the second on men who have sex with men. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1284184 / Thesis (Ph.D.) -- University of Adelaide, School of Population Health and Clinical Practice, 2007