Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / O número de mulheres jovens infectadas pelo HIV-1 vem crescendo desde o início da epidemia da aids, principalmente nos países em desenvolvimento, onde a frequência de gravidez é elevada. O desenvolvimento de estratégias para evitar a transmissão vertical tem aumentado o número de recém-nascidos não infectados nascidos de gestantes portadora do vírus. O objetivo da presente tese foi avaliar, in vivo e in vitro, o perfil de citocinas de neonatos não infectados, porém nascidos de mulheres infectadas pelo HIV-1. Os resultados demonstraram elevados níveis de citocinas pró-inflamatórias relacionadas ao fenótipo Th17, associadas à baixa produção de IL-10, tanto nos plasmas quanto nos sobrenadantes das culturas de células T ativadas obtidas do sangue do cordão umbilical de neonatos nascidos de gestantes infectadas pelo HIV-1 com cargas virais plasmáticas(PVL) detectáveis. De modo interessante, um perfil similar pró-inflamatório foi observado em amostras de sangue periférico de suas respectivas mães. Por outro lado, níveis elevados de IL-10, associados à reduzida produção de citocinas inflamatórias, foram dosados no sangue e nos sobrenadantes das culturas de células T ativadas de gestantes que controlavam a PVL, assim como de seus neonatos. Com relação à caracterização fenotípica das células T maternas produtoras de IL-10, a análise por citometria de fluxo demonstrou que essa citocina é majoritariamente produzida por células T CD4+Foxp3-. Curiosamente, a replicação viral in vitro do HIV-1 foi inferior nas culturas das gestantes infectadas pelo HIV-1 e foi relacionada aos efeitos inibitórios da IL-10 sobre a produção de TNF-α. Por fim, os neonatos não infectados expostosin utero à terapia antirretroviral (ART) apresentaram um menor peso ao nascer, e este achado foi inversamente correlacionado com os níveis periféricos maternos de TNF-α. Em conclusão, nossos achados sugerem que gestantes que conseguem controlar a PVL, e o incremento na produção de IL-10 materna possam favorecer a expansão das células Tr-1, as quais podem auxiliar em reduzir o risco de transmissão vertical do HIV-1 por reduzir a taxa de replicação viral. Por outro lado, outros resultados também apresentados aqui, apesar de preliminares, revelaram efeitos adversos da replicação viral e da ART em gestantes infectadas pelo HIV-1 no desenvolvimento funcional das células T de neonatos não infectados. Esses dados podem ajudar a explicar por que algumas dessas crianças apresentam elevado risco à morbidade e mortalidade devido a um estado basal de hipersensibilidade patológica. / The number of HIV-1-infected young women has been increasing since the beginning of the AIDS epidemic, mainly in developing countries, where the frequency of pregnancy among them is also elevated. The development of strategies for vertical transmission avoidance has enhanced the number of uninfected neonates born from infected mothers. The objective of the present study was to evaluate, in vivo and in vitro, the cytokine profile of uninfected neonates born from pregnant women infected with HIV-1.The results demonstrated high levels of proinflammatory cytokines related to Th17 phenotype associated with low IL-10 production, in plasma as well as in culture supernatants of activated T cells obtained from umbilical cord blood of neonates born from mothers infected with HIV -1 with plasma viral load (PVL) detectable.Interestingly, a similar pro-inflammatory cytokine profile was observed in peripheral blood samples from their respective mothers.On the other hand, high levels of IL-10 associated to reduced production of inflammatory cytokines were measured in blood and in the supernatants of activated T cells culturesfrom women that controlled the PVL, as well as their neonates.Regarding the phenotypic profile of pregnant women infected of HIV-1, the main T lymphocyte subset involved in producing IL-10 was CD4+Foxp3-. Interestingly, the in vitro HIV-1 replication was lower in cell cultures from pregnant patients, and it was related to the inhibitory effects of IL-10 on the production of TNF-α. Finally, ART-in utero-exposed neonates showed to be born with lower weight, and it was inversely correlated with maternal peripheral TNF-α level. In conclusion, the results suggest that pregnant women that are able to control the PVL, and the increment in the production of IL-10 may favor maternal Tr-1 cell expansion, which could help to reduce the risk of vertical transmission of HIV-1 by reducing the rate of viral replication.However, other results also presented here, although preliminary, have revealed adverse effects of viral replication, as well as the use of ART by pregnant women infected with HIV-1 in the development of functional T cells from uninfected newborns.These data may help to explain why some of these children have elevated risk of clinical morbidity and mortality due to a baseline state of pathological hypersensitivity.

Thesis (DTech (Mechanical Engineering))--Cape Peninsula University of Technology, 2012 / In this thesis, we investigate certain key aspects of mathematical modelling to explain the epidemiology of HIV/AIDS at the workplace and to assess the potential benefits of proposed control strategies. Deterministic models to investigate the effects of the transmission dynamics of HIV/AIDS on labour force productivity are formulated. The population is divided into mutually exclusive but exhaustive compartments and a system of differential equations is derived to describe the spread of the epidemic. The qualitative features of their equilibria are analyzed and conditions under which they are stable are provided. Sensitivity analysis of the reproductive number is carried out to determine the relative importance of model parameters to initial disease transmission. Results suggest that optimal control theory in conjunction with standard numerical procedures and cost effective analysis can be used to determine the best intervention strategies to curtail the burden HIV/AIDS is imposing on the human population, in particular to the global economy through infection of the most productive individuals. We utilise Pontryagin’s Maximum Principle to derive and then analyze numerically the conditions for optimal control of the disease with effective use of condoms, enlightenment/educational programs, treatment regime and screening of infectives. We study the potential impact on productivity of combinations of these conventional control measures against HIV. Our numerical results suggest that increased access to antiretroviral therapy (ART) could decrease not only the HIV prevalence but also increase productivity of the infected especially when coupled with prevention, enlightenment and screening efforts.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / O número de mulheres jovens infectadas pelo HIV-1 vem crescendo desde o início da epidemia da aids, principalmente nos países em desenvolvimento, onde a frequência de gravidez é elevada. O desenvolvimento de estratégias para evitar a transmissão vertical tem aumentado o número de recém-nascidos não infectados nascidos de gestantes portadora do vírus. O objetivo da presente tese foi avaliar, in vivo e in vitro, o perfil de citocinas de neonatos não infectados, porém nascidos de mulheres infectadas pelo HIV-1. Os resultados demonstraram elevados níveis de citocinas pró-inflamatórias relacionadas ao fenótipo Th17, associadas à baixa produção de IL-10, tanto nos plasmas quanto nos sobrenadantes das culturas de células T ativadas obtidas do sangue do cordão umbilical de neonatos nascidos de gestantes infectadas pelo HIV-1 com cargas virais plasmáticas(PVL) detectáveis. De modo interessante, um perfil similar pró-inflamatório foi observado em amostras de sangue periférico de suas respectivas mães. Por outro lado, níveis elevados de IL-10, associados à reduzida produção de citocinas inflamatórias, foram dosados no sangue e nos sobrenadantes das culturas de células T ativadas de gestantes que controlavam a PVL, assim como de seus neonatos. Com relação à caracterização fenotípica das células T maternas produtoras de IL-10, a análise por citometria de fluxo demonstrou que essa citocina é majoritariamente produzida por células T CD4+Foxp3-. Curiosamente, a replicação viral in vitro do HIV-1 foi inferior nas culturas das gestantes infectadas pelo HIV-1 e foi relacionada aos efeitos inibitórios da IL-10 sobre a produção de TNF-α. Por fim, os neonatos não infectados expostosin utero à terapia antirretroviral (ART) apresentaram um menor peso ao nascer, e este achado foi inversamente correlacionado com os níveis periféricos maternos de TNF-α. Em conclusão, nossos achados sugerem que gestantes que conseguem controlar a PVL, e o incremento na produção de IL-10 materna possam favorecer a expansão das células Tr-1, as quais podem auxiliar em reduzir o risco de transmissão vertical do HIV-1 por reduzir a taxa de replicação viral. Por outro lado, outros resultados também apresentados aqui, apesar de preliminares, revelaram efeitos adversos da replicação viral e da ART em gestantes infectadas pelo HIV-1 no desenvolvimento funcional das células T de neonatos não infectados. Esses dados podem ajudar a explicar por que algumas dessas crianças apresentam elevado risco à morbidade e mortalidade devido a um estado basal de hipersensibilidade patológica. / The number of HIV-1-infected young women has been increasing since the beginning of the AIDS epidemic, mainly in developing countries, where the frequency of pregnancy among them is also elevated. The development of strategies for vertical transmission avoidance has enhanced the number of uninfected neonates born from infected mothers. The objective of the present study was to evaluate, in vivo and in vitro, the cytokine profile of uninfected neonates born from pregnant women infected with HIV-1.The results demonstrated high levels of proinflammatory cytokines related to Th17 phenotype associated with low IL-10 production, in plasma as well as in culture supernatants of activated T cells obtained from umbilical cord blood of neonates born from mothers infected with HIV -1 with plasma viral load (PVL) detectable.Interestingly, a similar pro-inflammatory cytokine profile was observed in peripheral blood samples from their respective mothers.On the other hand, high levels of IL-10 associated to reduced production of inflammatory cytokines were measured in blood and in the supernatants of activated T cells culturesfrom women that controlled the PVL, as well as their neonates.Regarding the phenotypic profile of pregnant women infected of HIV-1, the main T lymphocyte subset involved in producing IL-10 was CD4+Foxp3-. Interestingly, the in vitro HIV-1 replication was lower in cell cultures from pregnant patients, and it was related to the inhibitory effects of IL-10 on the production of TNF-α. Finally, ART-in utero-exposed neonates showed to be born with lower weight, and it was inversely correlated with maternal peripheral TNF-α level. In conclusion, the results suggest that pregnant women that are able to control the PVL, and the increment in the production of IL-10 may favor maternal Tr-1 cell expansion, which could help to reduce the risk of vertical transmission of HIV-1 by reducing the rate of viral replication.However, other results also presented here, although preliminary, have revealed adverse effects of viral replication, as well as the use of ART by pregnant women infected with HIV-1 in the development of functional T cells from uninfected newborns.These data may help to explain why some of these children have elevated risk of clinical morbidity and mortality due to a baseline state of pathological hypersensitivity.

The purpose of this study is to explore and describe the challenges experienced by non-governmental organisations with regards to the roll-out of ART, with an aim to facilitate strategy development to overcome the challenges and enhance the success of ART rollout by the NGOs. A qualitative, exploratory and descriptive study was conducted. Data collection was done using in-depth semi-structured interviews. Three groups of respondents participated in the study; programme coordinators who directed and supervised ART programmes; doctors who were responsible for prescribing, monitoring and dealing with ART complications; and registered nurses who were responsible for monitoring, referring and providing nursing care to patients on ART. The findings revealed five broad areas of challenges namely; challenges related to sustainability, challenges related to adherence, challenges related to health systems, challenges related to stigma and challenges related to behavior. Of interest were the surge of whoonga and the infiltration of ART roll-out by crime and violence. / Health Studies / M.A. (Public Health)

The impact of HIV and AIDS has threatened to destroy the education sector in South Africa. This qualitative study set out to investigate the psychosocial problems and needs of educators infected with HIV and/or affected by HIV and AIDS in Johannesburg Inner City schools. The study explores and describes the need to develop and implement a comprehensive and holistic treatment, care and support programme for educators infected with HIV and/or affected by HIV and AIDS. This study also reviews HIV/AIDS policies and programmes implemented by the Department of Education to indicate that these interventions are not effective in addressing the problems and needs of these educators. Therefore, the study contends that the Department of Education should revise and reformulate these HIV/AIDS policies and programmes to cater for the needs of educators infected with HIV and/or affected by HIV and AIDS. Ten educators infected with HIV and/or affected by HIV and AIDS from two selected Johannesburg Inner City schools participated in this study. Phenomenological strategies and in-depth interviews were used to capture day-to-day personal life experiences of these educators. The findings of the study reveal that there is a need for an urgent response by the Department of Education to develop and implement treatment, care and support programmes for educators infected with HIV and/or affected by HIV and AIDS. / Sociology / M.A. (Social Behaviour Studies in HIV/AIDS)

M.A. (Public Health) / Anti-Retroviral Therapy (ART) adherence is a crucial component of the patient management framework for people living with Human Immune Deficiency Virus (HIV). Trait emotional intelligence is “the constellation of behavioural-dispositions and self-perceived abilities to recognise, process, and utilise emotion-laden information”. The purpose of the study was to determine whether there was a correlation between ART adherence behaviour and behavioural-dispositions related to trait emotional intelligence among HIV/AIDS infected people receiving ART at the regional public hospitals in Addis Ababa. The study used observational, analytical, and cross-sectional research design. The participants were selected through a proportionally stratified systematic random sampling method. Data collection was through a structured self-report questionnaire format. The findings showed that 79.1% had optimal ART adherence behaviour; 84.4% had average trait emotional intelligence. The research finding showed a statistically significant positive correlation between ART adherence behaviour and behavioural-dispositions related to trait emotional intelligence at (r =0.417, n=392, P<0.001). / Health Studies

The purpose of this study was to determine factors affecting non-adherence to Anti-retroviral therapy among AIDS patients. A cross sectional quantitative survey, was used. Structured interviews were conducted with 300 ART patients. Data were analysed using SPSS version 13 and presented in charts, graphs and frequency tables. Motivators of good adherence were identified as disclosure of HIV positive status to more than one person, frequent adherence counselling, self-efficacy to adhere to ART, positive interactions between patients and healthcare providers; and using an adherence partner. Barriers to adherence were forgetfulness, transportation costs to and from the clinic, time away from work and side effects. There was a strong positive correlation between adherence, CD4 counts and viral load. Adherence was closely tied to immunologic and virologic improvements. Respondents with poor adherence were likely to have unsuppressed viral loads (OR 12.98, 95%, CI 4.9-34). / Health Studies / Masters of Public Health

The impact of HIV and AIDS has threatened to destroy the education sector in South Africa. This qualitative study set out to investigate the psychosocial problems and needs of educators infected with HIV and/or affected by HIV and AIDS in Johannesburg Inner City schools. The study explores and describes the need to develop and implement a comprehensive and holistic treatment, care and support programme for educators infected with HIV and/or affected by HIV and AIDS. This study also reviews HIV/AIDS policies and programmes implemented by the Department of Education to indicate that these interventions are not effective in addressing the problems and needs of these educators. Therefore, the study contends that the Department of Education should revise and reformulate these HIV/AIDS policies and programmes to cater for the needs of educators infected with HIV and/or affected by HIV and AIDS. Ten educators infected with HIV and/or affected by HIV and AIDS from two selected Johannesburg Inner City schools participated in this study. Phenomenological strategies and in-depth interviews were used to capture day-to-day personal life experiences of these educators. The findings of the study reveal that there is a need for an urgent response by the Department of Education to develop and implement treatment, care and support programmes for educators infected with HIV and/or affected by HIV and AIDS. / Sociology / M.A. (Social Behaviour Studies in HIV/AIDS)

Anti-Retroviral Therapy (ART) adherence is a crucial component of the patient management framework for people living with Human Immune Deficiency Virus (HIV). Trait emotional intelligence is “the constellation of behavioural-dispositions and self-perceived abilities to recognise, process, and utilise emotion-laden information”. The purpose of the study was to determine whether there was a correlation between ART adherence behaviour and behavioural-dispositions related to trait emotional intelligence among HIV/AIDS infected people receiving ART at the regional public hospitals in Addis Ababa. The study used observational, analytical, and cross-sectional research design. The participants were selected through a proportionally stratified systematic random sampling method. Data collection was through a structured self-report questionnaire format. The findings showed that 79.1% had optimal ART adherence behaviour; 84.4% had average trait emotional intelligence. The research finding showed a statistically significant positive correlation between ART adherence behaviour and behavioural-dispositions related to trait emotional intelligence at (r =0.417, n=392, P<0.001). / Health Studies / M. A. (Public Health)

Adherence to long-term medications has remained a problem among adolescents worldwide. Antiretroviral therapy adherence is a wide-reaching challenge among HIV positive adolescents. The aim of this study is to explore and describe poor ART adherence among HIV positive adolescents in Maseru: influential factors and the need of social work support. Qualitative approach was used, following an explorative, descriptive and contextual research design. The research was conducted at BCMCOE Lesotho. Data was collected by using semi-structured in-depth interviews and purposive sampling was applied to select a sample of adolescents who are HIV positive and who have poor adherence to ART. Data was analysed according to the framework provided by Tesch (in Creswell 2003). Guba’s model (in Krefting 1991) was employed for data verification. Conclusions were drawn and recommendations were made about factors influencing adherence of adolescents to ART and support needed from social workers. / Social Work / M.A.(S.S.)