In the current studies we found that hep-ATIII treatment down-regulated NFkB after 7 days. This is important since the NFkB dimer consisting of p50 and RelA is considered to be the largest contributor to activation of HIV transcription and inflammation. Our second network was centered around ERK1/2 and seems to be dependent on PTGS2, an HIV inhibitory host cell factor ACET described earlier. Thus, another possible mechanism by which hep-ATIII might prevent HIV-induced dementia is through its anti-inflammatory effect since prostaglandins were found to block inflammation through inhibition of HIV-1 Tat-mediated ERK1/2 activation. There are several limitations to these studies. In our investigation of virus-induced cytotoxicity in the spleens of humanized mice, we have not characterized the specific cellular 7-Chlorokynurenic acid sodium salt populations that are preserved in contrast to those that are lost, nor have we determined the mechanism by which hep-ATIII may prevent cytotoxicity. We have not provided a mechanism for viral rebound after treatment with ET-ATIII. Our gene expression analyses suggest that the mechanism of ET-ATIII is through recruitment of innate antiviral mechanisms. Although it is unclear whether HIV can rapidly evolve resistance to host innate factors in such a rapid timeframe, we suspect that the rebound is most likely due to the clearance of ET-ATIII from the host, and hence loss of its suppressive activity. Our non-human primate pilot studies are limited by the number of animals available, but we believe provide justification for a larger scale trial. Clearly testing a more prolonged administration regimen is needed to more fully evaluate the safety and efficacy of ET-ATIII as an anti-HIV therapeutic. In conclusion, our data suggest that activated ATIII targeted to lymph nodes may have substantial in vivo activity against HIV-1. Further understanding of the mechanisms by which hep-ATIII interferes with HIV replication in lymphoid tissues might have important implications for the design of therapeutic strategies that harness the innate immune system for both its direct antiretroviral potential and its ability to modulate the adaptive immune response. Even though response to the first-line treatment is high, most patients relapse after the treatment. Recently, side populations of cancer cells with ABC-transporter activity and ability to efflux certain compounds have been identified in many different types of tumors, including ovarian cancer. These cells are referred to as cancer stem cells because of their many unique properties: they have self-renewal and differentiation capabilities and exhibit resistance to the effects of radiation and anticancer drugs.