Dans la première partie de ce travail, nous passons en revue les sujets qui ont fait l’objet d’essais thérapeutiques randomisés dans le domaine de la prévention et de la prise en charge de l’adulte infecté par le VIH en Afrique sub-saharienne. Nous en tirons deux conclusions : (i) que beaucoup de questions de recherche n’ont pas été explorées par des essais, soit parce qu’elles n’ont pas été jugées prioritaires, soit parce qu’un essai pour répondre à la question n’était pas jugé possible ; (ii) que les essais ayant des résultats positifs débouchent souvent eux même sur de nouvelles questions, notamment sur l’interprétation à donner à leurs résultats, les implications pratiques, les projections à long terme, et la réplicabilité dans différents contextes. Il arrive que ces questions paralysent les décisions. La question se pose donc d’utiliser au mieux les outils complémentaires aux essais thérapeutiques, incluant l’outil « modélisation ». Dans la deuxième partie, nous situons les modèles multi-états d’histoire naturelle de la maladie dans le spectre des différents modèles mathématiques utilisés en recherche médicale, et nous décrivons en détail un de ces modèles, le modèle « Cost Effectiveness of Preventing Aids Complication » (CEPAC) conçu aux USA, et développé puis appliqué ensuite dans la collaboration « CEPAC international » avec des équipes françaises, ivoirienne, Sud-Africaine et indienne pour des analyses cout-efficacité. Dans la troisième partie, nous utilisons le modèle CEPAC pour explorer deux questions : La première question porte sur le choix entre efavirenz, potentiellement tératogène, et la névirapine, pouvant être responsable d’une toxicité sévère, pour servir de base à la première ligne de traitement antirétroviral chez les femmes en âge de procréer en Afrique subsaharienne. En projetant à 10 ans la survie chez la mère et le nombre cumulé de malformations chez l’enfant, nous montrons que la tératogénicité de l’efavirenz devrait être 2,3 fois plus élevée que celle de la nevirapine pour que le nombre de malformations chez les enfants dont les mères ont pris de l’efavirenz soit supérieur au nombre de décès chez les femmes qui ont pris de la nevirapine. La deuxième question porte sur l’efficacité et le coût-efficacité de plusieurs stratégies thérapeutiques après l’échec de la deuxième ligne de traitement ARV chez des adultes en Côte d’Ivoire. Cette analyse montre que l’utilisation des médicaments ARV de troisième ligne serait dores et déjà non seulement efficace mais également coût-efficace en Côte d’Ivoire, si elle était utilisée dans une stratégie comportant une phase de renforcement intensif de l’adhérence avant décision de changement de ligne. En conclusion, nous proposons de définir en quatre groupes les situations dans lesquelles la modélisation peut aider la recherche clinique : (i) pour aider à la conception d’un essai clinique ; (ii) pour mettre en perspective les résultats d’essais cliniques, en les projetant à plus long termes ou dans différents contextes ; (iii) pour étudier une question pour laquelle un essai clinique n’est pas faisable ; (iv) pour stimuler la réflexion sur de nouvelles questions sur lesquelles il n’y a pas encore eu d’essai. En même temps qu’on expérimente l’utilisation pratique de ces modèles, il y a également une réflexion à avoir sur les aspects de validation, de transparence et de standardisation, notamment au moment de la publication des études, pour les rendre accessibles aux cliniciens et aux chercheurs qui ne sont pas familiers avec la modélisation. / In the first part of this work, we review the issues that have been the subject of randomized clinical trials in the field of prevention and care of HIV-infected adults in sub-Saharan Africa. From this research, we draw two conclusions: (i) many research questions have not been explored with clinical trials, either because they were not considered as a priority, or because conducting a trial was not a feasible way to answer the question; (ii) trials with positive results often lead to new issues, especially regarding interpretation of results, practical implications, long-term projections, and replication in different contexts. At times, these issues paralyze health decisions. The question therefore becomes how to best use tools that complement clinical trials, including "disease modelling" tools. In the second part of this work, we place multi-state models of natural history of disease within different mathematical models used in medical research. We describe, in detail, one of these models--the “Cost Effectiveness of Preventing Aids Complication” (CEPAC) model, designed in the USA and then developed and implemented by the “CEPAC-International” collaboration, which includes French, Ivorian, South African and Indian teams, to conduct cost-effectiveness analyses. In the third part, we use the CEPAC model to explore two questions: The first question is concerned with whether to use efavirenz, which is potentially teratogenic, or nevirapine, which can induce severe toxicity, in first-line antiretroviral regimen for women of child-bearing age in sub-Saharan Africa. Projecting at 10 years the survival of the mothers and the cumulative number of malformations in their children, we show that the teratogenicity of efavirenz would have to be 2.3 times higher than that of nevirapine for the additional number of defects in children whose mothers are taking efavirenz to be greater than the number of additional deaths among women who are taking nevirapine. The second question focuses on the effectiveness and cost-effectiveness of different treatment strategies after the failure on second-line antiretroviral therapy (ART) in HIV-infected adults in Côte d'Ivoire. This analysis shows that the use of third-line ART would be effective and cost-effective in Côte d'Ivoire, if used within a strategy that mandated an intensive adherence reinforcement intervention before deciding to switch patients to third-line. In conclusion, we define four situations within which modelling can help inform clinical research: (i) to assist the design of clinical trials, (ii) to put in perspective the results of clinical trials, by projecting the results in the long term or in different contexts, (iii) to study any questions for which a clinical trial is not suitable, (iv) to fuel the discussion on new issues for which testing has not yet be done. While we experiment with the practical use of these models, we also have to reflect on the validation, standardization, and transparency of the model, especially at the time of publication, to make sure studies are accessible to clinicians and researchers who are not familiar with modelling.

O trabalho é uma análise comparada de cinco mecanismos de política urbana praticados em quatro países diferentes: EUA, França, Colômbia e Brasil. Esses mecanismos têm como característica principal o financiamento de melhorias na infraestrutura urbana, com recursos gerados por parte da valorização imobiliária, e apropriados por meio desses mecanismos. São eles: Transfer of Development Rights (TDR) nos EUA, Leyes de la Plusvalia na Colômbia, Zones d´Aménagement Concertée (ZAC) na França, CEPACs e Outorga Onerosa em São Paulo, Brasil. O objetivo do trabalho é identificar princípios e regras comuns entre eles, e analisar suas diferenças mais significativas, e as razões para isso. Os mecanismos são apresentados individualmente e, em seguida, comparados quanto a suas características principais: histórico e objetivos de sua implantação, estrutura legal, método de formação do preço ou valor a ser pago, momento do pagamento e eficácia na geração de benefícios urbanísticos. / This work is a comparative analysis of five different mechanisms or urban policy as they are practiced in four different countries: the USA, France, Colombia and Brazil. The main characteristic these mechanisms have in common is the financing of improvements in the urban infrastructure with resources generated by the increase in value or real estate, and the corresponding capture part of that increase in value. The mechanisms analyzed are: Transfer of Development Rights (TDR) in the USA, Leyes de la Plusvalia, in Colombia, Zones d\'Aménagement Concertée (ZAC) in France, Certificados de Potencial Adicional de Construção (CEPACs) and Outorga Onerosa do Direito de Construir, São Paulo, Brazil. The objective of this work is to identify the principles and rules that they share, analyze the most relevant differences and the reasons for those differences. Each of the mechanisms is presented individually, followed by a comparison of their main characteristics: its objective and history, legal structure, price or value formation, moment of payment, and its effectiveness in generating urban improvement.

O trabalho é uma análise comparada de cinco mecanismos de política urbana praticados em quatro países diferentes: EUA, França, Colômbia e Brasil. Esses mecanismos têm como característica principal o financiamento de melhorias na infraestrutura urbana, com recursos gerados por parte da valorização imobiliária, e apropriados por meio desses mecanismos. São eles: Transfer of Development Rights (TDR) nos EUA, Leyes de la Plusvalia na Colômbia, Zones d´Aménagement Concertée (ZAC) na França, CEPACs e Outorga Onerosa em São Paulo, Brasil. O objetivo do trabalho é identificar princípios e regras comuns entre eles, e analisar suas diferenças mais significativas, e as razões para isso. Os mecanismos são apresentados individualmente e, em seguida, comparados quanto a suas características principais: histórico e objetivos de sua implantação, estrutura legal, método de formação do preço ou valor a ser pago, momento do pagamento e eficácia na geração de benefícios urbanísticos. / This work is a comparative analysis of five different mechanisms or urban policy as they are practiced in four different countries: the USA, France, Colombia and Brazil. The main characteristic these mechanisms have in common is the financing of improvements in the urban infrastructure with resources generated by the increase in value or real estate, and the corresponding capture part of that increase in value. The mechanisms analyzed are: Transfer of Development Rights (TDR) in the USA, Leyes de la Plusvalia, in Colombia, Zones d\'Aménagement Concertée (ZAC) in France, Certificados de Potencial Adicional de Construção (CEPACs) and Outorga Onerosa do Direito de Construir, São Paulo, Brazil. The objective of this work is to identify the principles and rules that they share, analyze the most relevant differences and the reasons for those differences. Each of the mechanisms is presented individually, followed by a comparison of their main characteristics: its objective and history, legal structure, price or value formation, moment of payment, and its effectiveness in generating urban improvement.