This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. We have previously developed a SIV-infected Chinese rhesus macaque (ChRM) model for HIV-infected long-term nonprogressors (LTNP). By using this model, we have also demonstrated that the gastrointestinal tract, especially the colon, is a major reservoir for LTNP even when plasma viral load is undetectable by standard assay. We are using this model to further test the hypothesis that ChRM of SIV infection is a better model than other nonhuman primates for studies of tissue reservoirs on antiretroviral therapy, for evaluation of new strategies of viral eradication and immune restoration. Currently, we are conducting antiretroviral therapy (ART) in chronically SIV-infected ChRM. Animals were treated with PMPA/FTC and L-870812 daily for 2 months. Our results showed that plasma viral loads were reduced to 30 copies/ml in animals receiving ART. Immune activation of T cells in the gut was reduced in the first month of ART. Both jejunal and colonic mucosal memory CCR5+CD4+ T cells increased significantly and they were positively correlated during treatment. Moreover, restoration of these cells was inversely correlated with immune activation. Our studies indicate that combination ART is effective to suppress viral replication, reduce immune activation, and benefit to immune restoration in the gut. Further addition of protease inhibitors or other new regimens are to be evaluated if further reduction of residual viral replication and reservoir can be achieved in the intestinal mucosa.
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