D Wodarz

..Issues concerning the timing and duration of treatment are discussed. The CTL kinetics during drug therapy also provide new insights into the principles underlying the emergence of drug-resistant strains during the course of treatment...

..These insights are important for understanding the disease process itself and for designing effective treatment regimes...

..We discuss our findings in the context of specific viral infections and use our model to interpret empirical data...

..We observe that genetic instability is of value early in tumorigenesis but becomes a liability later. This is because instability decreases the fitness of the angiogenic tumor once it has become established...

..In particular, the models offer further suggestions for the development of treatment regimes aimed at achieving immunological control of HIV infection which has been shown to crucially depend on the availability of helper cell responses...

..The models precisely define conditions required for successful therapy. They identify the parameters that need to be measured and modulated to evaluate and refine the existing therapy regimes...

..These results have important implications for vaccination and treatment strategies directed against viral infections...

..We show how mathematical models can help us devise therapy regimens that can restore CTL memory in HIV patients and result in long-term immunological control of the virus in the absence of life-long treatment...

..Whether such treatment regimes would lead to long-term immunologic control deserves investigation under carefully controlled conditions...

..Based on our models we suggest conceptual treatment regimes which ensure establishment of CTL memory. This would allow the immune response to control HIV in the long term in the absence of continued therapy...

..However, according to the model, fast viral replication can result in the evolution of virus strains that are susceptible to chemokine-mediated inhibition of viral replication...

..We propose a method to test this idea, and develop a framework that is readily applicable to treatment of other infections...

..Virus-mediated impairment of specific CTL production in HIV-1 infection can account for the negative correlation observed...

..We show how mathematical models can help us devise therapy regimes that can restore CTL memory in HIV-infected patients and result in long-term immunological control of the virus in the absence of lifelong treatment...

..We apply the model to study the role of CTL in cancer initiation, cancer evolution/progression, and therapeutic vaccination against cancers...

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..Thus, while in the absence of pathogen diversity memory is always expected to evolve to a long duration, under specific circumstances, memory can evolve toward shorter durations in the presence of pathogen diversity...

..Virus evolution can shift this balance towards pathology over time. Theoretical results are discussed in the context of published data...

..If a high multiplicity of infection is used, the virus that appears most efficient in this evaluation can be least efficient at eradicating the cancer in vivo. Theoretical results are discussed in the context of experimental data...

..Although the therapy regimes explored here also have implications for HIV, virus-mediated destruction of specific immune cells renders success unlikely during the chronic phase of the infection...

..Finally, we show how mathematical models can be used to understand correlates of long-term immunological control of HIV, and to design therapy regimes that convert a progressing patient into a state of long-term non-progression...

..We discuss these results in the context of data from murine virus infections and explore implications for virus dynamics in CD4 helper-deficient hosts...

..This model provides valuable information and may help to explain the inflation of CMV specific CD8+T cells seen in humans as they age...

..We introduce a mathematical model of these dynamics and show simple optimal control based strategies which motivate this approach...

..Using mathematical models, we investigate the effect of cellular quiescence on the outcome of therapy with targeted small molecule inhibitors...

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..One possibility is that the ability of multiple virus particles to infect the same cell (coinfection) might be a pre-requisite for the emergence of the cytopathic strain SIVMne170 as the disease progresses...

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..The 7-10 programmed cell divisions observed in vivo might be an optimization of this trade-off. We also discuss the conditions under which the program does or does not require CD4 T-cell help for clearance...

..Thus, although a T cell vaccine might work against a high dose exposure, it might fail when exposed against to a low-dose exposure. This limits, we argue, the efficacy of T cell-based vaccines...

..These findings are consistent with mathematical models that predict virus-host dynamics in this, and other, models of infection...

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..The models presented are related to the concept of apparent competition, and our results are discussed in relation to both theoretical and empirical studies...

..Instead, it arises for other reasons, such as environmental factors, and is subsequently fine-tuned by selection to minimize the time to further cancer progression by means of the inactivation of TSP genes...

..Drug resistance is much more likely to be a problem in HIV than in acute and self-limiting infections...

..The models help to identify differences in the experimental protocols which could explain the seemingly contradictory observations...

..According to these arguments, an inverse correlation between the level of attenuation and the level of protection is expected, and this has indeed been observed in experimental data...