Grant: Catalyst Grant: HIV/AIDS and Co-morbidities - Biomedical/Clinical

Both AIDS and tuberculosis (TB) represent independent pandemics, affecting a very large number of humans. In the last decade, there has been an enormous expansion of the number of patients with active TB, a phenomenon which is largely attributable to HIV-infection. TB/HIV co-infection is deadly. TB represents the leading cause of death in HIV-1 infected patients. Moreover, HIV infection significantly increases the rate of rapid TB progression in new TB infection and multiplies by ~100-fold the risk of reactivation of latent TB. In addition, even the avirulent BCG vaccine, given to children for vaccination against TB, can induce a severe BCG disease in HIV-1 infected children. There is surprisingly very little known about the basis of this huge co-infection problem. As usual in medicine, for understanding this co-infection, animal models will be required. Already, a few primate TB models, infectable with a primate virus similar to HIV, have been developed, but they are not widely available nor used much and are expensive. More importantly, many critical experiments cannot be done on these large animals. Mouse models are widely used for TB research and have contributed enormously to this field. But they have not been used for TB research in the context of HIV-induced AIDS. We are proposing here to develop mouse models of TB/HIV co-infection. Over the last few years, we have generated and developed mouse models of AIDS. These mice show a very similar AIDS-like disease, as the one observed in HIV-1 infected individuals. We hypothesize that these Tg mice represent an adequate model for studies of TB/HIV interactions. We propose here to use them to develop mouse models of HIV/TB co-infection.