HIV infects over 33 million people worldwide with a new infection occurring every 9 seconds. Sex is the primary mode of transmission and the majority of new infections occur during unprotected sexual contact between an HIV-infected individual and an uninfected sexual partner(s) since HIV infected individuals tend to shed virus in their genital secretions. The infectiousness of an individual is closely tied to the amount of virus in blood, which is closely associated with HIV levels shed in semen or vaginal fluid or rectal secretions. Although, Highly Active Antiretroviral Therapy (HAART) is associated with complete suppression of HIV RNA in blood to undetectable levels, the impact of HAART on semen HIV RNA levels is less clear. I evaluated the correlation between systemic and mucosal HIV-specific CD8+ T cell immune responses and HIV RNA levels in blood and semen. Overall, there was a strong positive correlation between HIV RNA levels in blood and semen. Neither systemic nor mucosal (in semen) HIV-specific CD8+ responses were associated with HIV RNA levels in blood or semen, in fact CD8+ T cell immune responses in semen correlated with increased HIV RNA levels in semen. Furthermore, inflammatory cytokines (IL-6, and IL-8) CMV levels in semen were associated with increased semen HIV RNA shedding. HAART initiation was associated with complete suppression of HIV viremia, but a significant proportion of individuals on suppressive HAART continue to shed HIV RNA in semen even after 6 months, and this isolated virus was infectious and often present at high levels (> 5000 copies/mL). Nevertheless, long-term HAART was associated with complete immune reconstitution of CD4+ T cells in the sigmoid colon of HIV-infected individuals on long-term therapy. These findings demonstrate that neither systemic nor mucosal HIV-specific CD8+ responses, when assayed with IFN- production as an endpoint, were associated with reduced HIV RNA levels in blood or semen. Semen HIV RNA levels did correlate with local inflammatory cytokines and CMV reactivation. Furthermore, despite effective HAART a significant proportion of HIV-infected men continued to shed HIV RNA in semen. However, long-term completely suppressive HAART was associated with complete immune reconstitution of the sigmoid colon.

HIV infects over 33 million people worldwide with a new infection occurring every 9 seconds. Sex is the primary mode of transmission and the majority of new infections occur during unprotected sexual contact between an HIV-infected individual and an uninfected sexual partner(s) since HIV infected individuals tend to shed virus in their genital secretions. The infectiousness of an individual is closely tied to the amount of virus in blood, which is closely associated with HIV levels shed in semen or vaginal fluid or rectal secretions. Although, Highly Active Antiretroviral Therapy (HAART) is associated with complete suppression of HIV RNA in blood to undetectable levels, the impact of HAART on semen HIV RNA levels is less clear. I evaluated the correlation between systemic and mucosal HIV-specific CD8+ T cell immune responses and HIV RNA levels in blood and semen. Overall, there was a strong positive correlation between HIV RNA levels in blood and semen. Neither systemic nor mucosal (in semen) HIV-specific CD8+ responses were associated with HIV RNA levels in blood or semen, in fact CD8+ T cell immune responses in semen correlated with increased HIV RNA levels in semen. Furthermore, inflammatory cytokines (IL-6, and IL-8) CMV levels in semen were associated with increased semen HIV RNA shedding. HAART initiation was associated with complete suppression of HIV viremia, but a significant proportion of individuals on suppressive HAART continue to shed HIV RNA in semen even after 6 months, and this isolated virus was infectious and often present at high levels (> 5000 copies/mL). Nevertheless, long-term HAART was associated with complete immune reconstitution of CD4+ T cells in the sigmoid colon of HIV-infected individuals on long-term therapy. These findings demonstrate that neither systemic nor mucosal HIV-specific CD8+ responses, when assayed with IFN- production as an endpoint, were associated with reduced HIV RNA levels in blood or semen. Semen HIV RNA levels did correlate with local inflammatory cytokines and CMV reactivation. Furthermore, despite effective HAART a significant proportion of HIV-infected men continued to shed HIV RNA in semen. However, long-term completely suppressive HAART was associated with complete immune reconstitution of the sigmoid colon.

This thesis was undertaken to assess the characteristics of individuals who smoke crack cocaine and to examine the health-related risks and healthcare needs of this population. A literature review of 147 published articles was conducted to synthesize evidence regarding behaviours associated with crack use and to assess the risks of disease transmission through crack smoking behaviours. Qualitative interviews were subsequently conducted with thirty Ottawa residents who smoke crack to learn about their experiences with healthcare and harm reduction services. Results identified barriers related to accessing primary healthcare and drug treatment programming among people who smoke crack and gaps within existing harm reduction services. Individuals who smoke crack represent a marginalized population who are often missed through traditional health promotion and harm reduction programming. There is a need for increased coverage of current programming and a reduction of factors which currently hinder the delivery and effectiveness of crack-specific harm reduction programs.

This thesis is based on the use of mathematical theories, modelling, and simulations to study the transmission dynamics of HIV/AIDS in the presence of PrEP (pre-exposure prophylaxis) in the MSM (men who have sex with men) population in the United States. A new deterministic model for HIV/AIDS that incorporates PrEP is designed and used to assess the population-level impact of the use of PrEP on the transmission dynamics within an MSM population. Conditions for the effective control (or elimination) and persistence of HIV/AIDS in the MSM population are determined by rigorously analyzing this model. Uncertainty and sensitivity analysis is carried out to determine the effect of the uncertainties in the parameter values on the response variable (the associated reproduction number) and to identify the top-five parameters that have the most effect on the disease transmission dynamics. Numerical simulations show that HIV burden decreases with increasing PrEP coverage. / October 2015

This thesis was undertaken to assess the characteristics of individuals who smoke crack cocaine and to examine the health-related risks and healthcare needs of this population. A literature review of 147 published articles was conducted to synthesize evidence regarding behaviours associated with crack use and to assess the risks of disease transmission through crack smoking behaviours. Qualitative interviews were subsequently conducted with thirty Ottawa residents who smoke crack to learn about their experiences with healthcare and harm reduction services. Results identified barriers related to accessing primary healthcare and drug treatment programming among people who smoke crack and gaps within existing harm reduction services. Individuals who smoke crack represent a marginalized population who are often missed through traditional health promotion and harm reduction programming. There is a need for increased coverage of current programming and a reduction of factors which currently hinder the delivery and effectiveness of crack-specific harm reduction programs.

>Magister Scientiae - MSc / The influx of infecteds into a population plays a critical role in HIV transmission. These infecteds are known to migrate from one region to another, thereby having some interaction with a host population. This interactive mobility or migration causes serious public health problems. In a very insightful paper by Shedlin et al. [51], the authors discover risk factors but also beneficial factors with respect to fighting human immunodeficiency virus (HIV) transmission, in the lifestyles of immigrants from different cultural backgrounds. These associated behavioral factors with cross-cultural migrations have not received adequate theoretical a attention. In this dissertation we use the compartmental model of Bhunu et al. [6] to form a new model of the HIV epidemic, to include the effect of infective immigrants in a given population. In fact, we first produce a deterministic model and provide a detailed analysis. Thereafter we introduce stochastic perturbations on the new model and study stability of the disease-free equilibrium (DFE) state. We investigate theoretically and computationally how cross-cultural migrations and public health education impacts on the HIV transmission, and how best to intervene in order to minimize the spread of the disease. In order to understand the long-time progression of the disease, we calculate the threshold parameter, known as the basic reproduction number, R0. The basic reproduction number has the property that if R0 is sufficiently small, usually R0 < 1, then the disease eventually vanishes from the population, but if R0 > 1, the disease persists in the population. We study the sensitivity of the basic reproduction number with respect to model parameters. In this regard, if R0 < 1, we show that the DFE is locally asymptotically stable. We also show global stability of the DFE using the Lyapunov method. We derive the endemic equilibrium points of our new model. We intend to counteract the negative effect of the influx of infecteds into a population with educational campaigns as a control strategy. In doing so, we employ optimal control theory to find an optimal intervention on HIV infection using educational campaigns as a basic input targeting the host population. Our aim is to reduce the total number of infecteds while minimizing the cost associated with the use of educational campaign on [0, T ]. We use Pontryagin’s maximum principle to characterize the optimal level of the control. We investigate the optimal education campaign strategy required to achieve the set objective of the intervention. The resulting optimality system is solved numerically using the Runge-Kutta fourth order method. We present numerical results obtained by simulating the optimality system using ODE-solvers in MATLAB program. We introduce randomness known as white noise into our newly formed model, and discuss the almost sure exponential stability of the disease-free equilibrium. Finally, we verify the analytical results through numerical simulations.

This thesis was undertaken to assess the characteristics of individuals who smoke crack cocaine and to examine the health-related risks and healthcare needs of this population. A literature review of 147 published articles was conducted to synthesize evidence regarding behaviours associated with crack use and to assess the risks of disease transmission through crack smoking behaviours. Qualitative interviews were subsequently conducted with thirty Ottawa residents who smoke crack to learn about their experiences with healthcare and harm reduction services. Results identified barriers related to accessing primary healthcare and drug treatment programming among people who smoke crack and gaps within existing harm reduction services. Individuals who smoke crack represent a marginalized population who are often missed through traditional health promotion and harm reduction programming. There is a need for increased coverage of current programming and a reduction of factors which currently hinder the delivery and effectiveness of crack-specific harm reduction programs.

Philosophiae Doctor - PhD / In the decade since first identified, the Acquired Immunodeficiency syndrome (AIDS) has become a serious global disease. The nature of the Human Immunodeficiency Virus (HIV) that causes AIDS, whereby a carrier may be asymptomatic yet remain infectious, has enabled its dramatic spread. The number of AIDS cases is increasing exponentially, averaging a doubling time of between 8-15 months indifferent countries. Of the millions of HIV carriers, it is now estimated that all will eventually go on to develop full-blown AIDS and probably die within 15 years. Unlike other infectious diseases, there is currently no known vaccine or cure. Further, HIV is now virtually completely dependent on volitional sexual behaviours for transmission to occur. It is therefore an entirely preventable disease. However, since the behaviours that contribute to HIV-transmission are influenced by biological, psychological, and social factors, their alteration in line with safer sexual practices has been shown to be considerably complex and difficult. Intervention strategies that have relied on imparting knowledge about the disease have achieved limited success in influencing behaviour change. Unsafe sexual practices, and the risk of HIV-infection, often continue even when knowledge regarding prevention is adequate. It has therefore become apparent that other variables intrude which may mediate between knowledge acquisition, attitude formation, and consequent sexual behaviours. There appear to be no models which adequately explain the complexities in this area, and which enable adequate intervention strategies to be developed. The present study was undertaken to redress this problem, and to explore those variables that mediate in the area. Various psychological and social factors appear to be implicated in influencing sexual attitudes and behaviours. In order to adequately test the impact of psychosocial variables that were found to have significant associations in an exploratory study, a measuring instrument was developed. The AIDS Psychosocial Scale was statistically validated using content, frequency, factor, and reliability analyses and included psychological factors of self concept, defenses of denial, repression, and rationalisation, perceived empowerment in the form of locus of control and self efficacy, and the social factor of peer pressure susceptibility. The impact of these psychosocial variables on indices of knowledge, condom attitude, and sexual practices, and on other epidemiological variables was tested using a sample of students at the University of the Western Cape (n=308). Results indicated a number of correlational and causal links between variables, confirming the mediational role psychosocial factors have in influencing knowledge acquisition, attitude formation, and behaviour outcome. A profile of lower self concept, higher defenses, lower self-efficacy, more external locus of control, and higher peer pressure susceptibility emerged which was associated with poorer knowledge, more negative attitudes, and higher unsafe sex. Based on this study, a model of psychosocial mediation is developed and its implications for intervention strategies discussed.

Mother-to-infant vertical transmission of HIV usually occurs during pregnancy, labor, delivery or breastfeeding. It is the third leading cause of transmission of HIV after sexual intercourse and blood transfusions. In 2008, 12 million women aged 15 years and above were anticipated to be living with HIV in countries within Sub-Saharan Africa. In this study, the association between parental HIV knowledge, attitudes and risk reduction practices, and HIV vertical transmission in Kenya were explored. The health belief model was used to help understand and interpret the findings. For this quantitative study, data were collected via surveys from 212 participants in 3 HIV clinics in Kenya. Data were analyzed using descriptive and inferential statistics. Around 45% of respondents lacked knowledge on key aspects of Prevention of Mother to Child Transmission (PMTCT) of HIV particularly on expressing and heat treating milk from HIV positive mothers to make it safe for their babies. About 65% of Participants had awareness towards Mother to Child Transmission (MTCT) of HIV. Logistic regression showed no association between socioeconomic factors and parental knowledge on MTCT of HIV. Logistic modeling found that there was association between attitude and MTCT, revealing that attitude increased the likelihood to influence MTCT. Being married was associated with reduced risk of MTCT of HIV. The overall results indicated gaps in knowledge and information packaging. The potential positive social change implication of this study is that factors related to HIV vertical transmission identified in this study might be utilized to develop and implement HIV prevention strategies to reduce HIV vertical transmission and decrease associated morbidity and mortality among this vulnerable population.

A dissertation submitted to the Faculty of Health Sciences, University of Witwatersrand, Johannesburg in fulfillment of the requirements for the degree of Master of Science in Medicine, Johannesburg , 2013 / South Africa’s Prevention of Mother-to-Child Transmission (PMTCT) programme is critical for eliminating vertical HIV transmission and reducing infant mortality. Early treatment of HIV-infection to curb infant deaths requires earlier diagnostic testing than the currently recommended six-week test. This study describes the continuum of PMTCT care at a Johannesburg hospital to identify interventions for improvement and investigates birth HIV testing for infants. Data from a cohort study at the hospital evaluating diagnostic assays in HIV-exposed infants were collated with routine clinical data, validated and analysed. Among 838 mother-infant pairs, 38% of mothers attended antenatal clinics early enough to receive optimal antenatal prophylaxis. Only 72% of infants accessed six-week testing at the hospital; a further 10% underwent testing elsewhere. Of 38 HIV-infected infants, 29 were infected in-utero and could have been identified at birth (sensitivity of 76.3% for birth testing), compared to only 26 (68%) diagnosed by six-week testing at the hospital. Majority (88%) of these 26 infants accessed antiretroviral therapy, but treatment was only initiated at a median age of 16.0 weeks and 43% of HIV-infected infants who initiated treatment had defaulted or died before the end of the study. Mathematical modelling demonstrated that birth testing would be superior to a six-week test to maximise infants diagnosed and life years saved, with the ideal algorithm being a birth and ten-week test. The PMTCT programme can be enhanced by earlier antenatal care for women and earlier infant diagnosis. Birth testing would diagnose HIV-infection before infants die or default from the PMTCT programme, thereby enabling effective monitoring of MTCT, and would allow earlier treatment initiation to reduce early infant mortality.