Indiana University-Purdue University Indianapolis (IUPUI) / Background: Many authors have indicated that HIV-infected patients mortality risk is higher immediately following the start of Antiretroviral Therapy. However, mortality rate of HIV-infected patients is expected to decrease after starting Antiretroviral Therapy (ART) potentially complicating accurate statistical estimation of patient survival and, more generally, effective monitoring of the evolution of the worldwide epidemic. Method: In this thesis, we determine if mortality of HIV-patients increases or decreases after the initiation of ART therapy using flexible survival modelling techniques. To achieve this objective, this study uses semi-parametric statistical models for fitting and estimating survival time using different covariates. A combination of the Weibull distribution with splines is compared to the usual Weibull, exponential, and gamma distribution parametric models, and the Cox semi-parametric model. The objective of this study is to compare these models to find the best fitting model so that it can then be used to improve modeling of the survival time and explore the pattern of change in mortality rates for a cohort of HIV-infected patients recruited in a care and treatment program in Uganda. Results: The analysis shows that flexible survival Weibull models are better than usualoff-parametric and semi-parametric model fitting according to the AIC criterion. Conclusion: The mortality of HIV-patients is high right after the initiation of ART therapy and decreases rapidly subsequently.

Orientador: Liciana Vaz de Arruda Silveira / Resumo: Nas pesquisas clínicas, o método usado para analisar os fatores que contribuem para a mortalidade relacionada aos mais diversos tipos de desfecho é a análise de sobrevivência. Na pesquisa clínica há mais de um resultado possível durante o acompanhamento dos dados de sobrevivência, estes são conhecidos como eventos competitivos. Na ocorrência dos eventos em que a morte é considerada um evento censurado, o modelo de risco proporcional de Cox pode ser empregado para estimar os efeitos das covariáveis sobre o risco. Entretanto, o efeito sobre o risco não pode ser diretamente afetado pela função de incidência acumulada (FIA). Assim, de maneira geral, o presente estudo teve por objetivo fazer uma abordagem dos métodos de análise de sobrevida nos aspectos paramétricos de modelos flexíveis para riscos competitivos, e aplicá-los a uma coorte do Sul da Itália, para avaliar os riscos de óbito para câncer gastrointestinal e outras causas. Trata-se de um estudo observacional retrospectivo, com um período de seguimento de dez anos, realizado em duas coortes, totalizando 2.623 indivíduos selecionados segundo a lista de eleitores dos municípios Castellana Grotte e Putgnano, na Itália. Os modelos flexíveis para riscos competitivos foram usados para avaliar as distribuições acumuladas de incidência específica por causa. Observou-se que os indivíduos com câncer gastrointestinal adeptos da dieta mediterrânea apresentam um risco constante e menor de morrer, especialmente nas etapas inicial e fina... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: In clinical research, the method used to analyze the factors that contribute to mortality related to the most diverse types of outcome is the survival analysis. In clinical research there is more than one possible outcome during monitoring of survival data, these are known as competitive events. In the occurrence of events in which death is considered a censored event, the Cox proportional hazard model can be used to estimate the effects of covariates on risk. However, the effect on risk can not be directly affected by the cumulative incidence function (FIA). Thus, in general, the present study aimed to analyze the methods of survival analysis in the parametric aspects of flexible models for competitive risks, and to apply them to a cohort in the South of Italy to evaluate the risk of death for gastrointestinal cancer and other causes. This is a retrospective observational study with a follow-up period of ten years, carried out in two cohorts, totaling 2,623 individuals selected according to the list of voters of the municipalities Castellana Grotte and Putgnano, Italy. Flexible models for competitive risks were used to evaluate cumulative distributions xiii of specific incidence by cause. It was observed that individuals with gastrointestinal cancer adherents of the Mediterranean diet present a constant and lower risk of dying, especially in the initial and final stages of the follow-up, whereas this effect is less pronounced in individuals who did not adhere to the aforemen... (Complete abstract click electronic access below) / Doutor