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Conference
"Adjuvant Therapies" Dr. Giuseppe Pantaleo (biography) English - 2003-03-30 - 39 minutes
Summary : A fundamental turning point in the fight against HIV-1 Infection has been not only the development of antiviral drugs able to target different components of HIV-1 but more importantly, the understanding that multiple therapeutic strategies are necessary to control effectively HIV-1 replication. In fact, mono or bi-therapy approaches have minimal or no impact in controlling HIV-1 replication and disease. The development of triple combination therapies has led to effective control of virus replication and has had a dramatic impact on the progression of HIV-1 disease with a major reduction in morbidity and mortality. However, even though anti-retroviral therapy remains a fundamental component of the global therapeutic strategy against HIV-1 infection, the potential contribution of antiretroviral to the correction of the immunologic abnormalities is extremely limited. Antiretroviral therapy is capable of restoring CD4 T cell counts from a quantitative standpoint in patients with chronic infection but seems to have little impact on the restoration of an effective HIV-1-specific immune response. Therefore, the additional current challenge is to develop strategies that may correct the immunologic defects. The strategies of immune-based interventions that have received particular attention are those aimed at augmenting HIV-1 Specific immunity after immunization with virus subunits (virus proteins) and/or virus vector expressing different HIV-1 Proteins. These immunization strategies are also known as therapeutic vaccine and their main objective, at least in patients with chronic infection, has to be the development of de novo immune responses. Since the type of immune response already present is not able to control HIV-1 replication and all the evidences indicate that this immune response is extremely vigorous, at least with regard to the CD8 T cells, it is unlikely that a quantitative increment of the potency will confer a protective capacity to the immune response. In particular it is fundamental to stimulate HIV-1-specific CD4 helper T cell responses that are absent and/or severely impaired in patients with chronic infection. The restoration of CD4 helper T cells, e.g. therefore of the virus-specific CD4 T cells that function as precursors for the other populations of memory T cells, likely may insure the continuous replenishment of the population of memory CD4 T cells with effector function and the complete maturation of virus-specific memory CD8 T cells by the optimal secretion of factors such as IL-2 and IL-15.
In addition to these conventional strategies of immune-based interventions, it may be interesting to develop strategies that may selectively target other immunologic abnormalities such as the massive immune activation that is extremely deleterious since it further amplifies the immune dysfunction and at the same time supports optimal virus production. Therefore, it is possible that suppression of immune activation in certain phases of HIV-1 infection may result in both virologic and immunologic beneficial effects.
In conclusion, there is a major need for the development of a multi-strategic approach to potentially achieve effective control of HIV-1 infection. Immune-based interventions can be complementary to anti-retroviral therapy that remains the primary treatment intervention in order to achieve effective suppression of virus replication.
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