Immune Activation and AIDS Pathogenesis

Donald L Sodora; Guido Silvestri

Disclosures

AIDS. 2008;22(4):439-446. 

In This Article

What experiments should be done to further test the immune activation hypothesis?

There is ample consensus among investigators that further experimentation - particularly in vivo studies conducted in the simian model of infection - is needed to ascertain and better characterize the pathogenic role of immune activation during HIV infection. Ideally, the best type of 'experiment' would involve treatment of SIV-infected macaques with drugs that either reduce or, alternatively, heighten the level of immune activation in vivo and then assess their effects on immune function and disease progression. Such experimental strategy should include treatment of SIV-infected macaques with TLR antagonists, chloroquine, or antibiotics. An additional interesting approach would be to determine whether artificially increasing the level of immune activation in natural SIV hosts such as SM and AGM (in which low immune activation is typically associated with a non-pathogenic infection) would result in signs of immunodeficiency. In this view, an interesting possibility is testing the 'bacterial translocation' hypothesis in SM and/or AGM by the administration of one or more bacterial TLR ligands to these animals during SIV infection. For studies aimed at modulating (i.e., increasing or decreasing) the HIV/SIV associated immune activation, the type, dose, and route of administration of the intervention agents, as well as the timing (acute versus chronic infection) are all important factors that require careful consideration in the design of these future experiments. More generally, it will be important to conduct studies aimed at determining which of the available models of pathogenic SIV infection in macaques (i.e., which virus, which species, etc.) demonstrates a degree of immune activation and disease progression that best resembles HIV infection in humans. Recent interesting comparative studies of Indian and Chinese rhesus macaques indicate that Indian rhesus tend to progress more rapidly to overt disease compared to Chinese rhesus.[95] The pattern of immune activation observed in Chinese macaques (particularly as assessed by the relative expansion of CD4CCR5 T cells) also suggests that infection of these animals may be more representative of HIV infection.[96]

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