Thus, the concept of HIV entry through one of the two coreceptors ����separately���� needs to be revised. Indeed, our in vitro results are also consistent with others obtained in vivo: from the A4001029-study, showing that maraviroc is effective also in some patients carrying dual-tropic viruses, from a recent case-report that demonstrates the ability of maraviroc to inhibit dual-R5 viruses in a dual/mixed HIV-1-infected patient. The efficiency of maraviroc to inhibit HIV-1 replication in macrophages can have important pathogenic and clinical implications, in particular by reducing the dissemination of HIV in different body compartments and cellular reservoirs. This is particularly relevant in the central nervous system where maraviroc is known to efficiently penetrate. In addition, macrophages at vaginal level have been shown to be permissive to HIV infection after the virus has translocated across the epithelium. The high activity of maraviroc against macrophages might also contribute in controlling mucosal HIV-1 infection in sexual-transmission. By analysing in vitro activity of CXCR4-antagonist AMD3100, we found the ability of this drug to inhibit the replication of pure- X4 and also some dual/mixed-tropic viruses in both PBMC and MDM. Again this is in line with another in vivo study, showing the ability of AMD3100 to suppress both X4-tropic and certain dual-tropic variants, that use more efficiently the CXCR4 coreceptor than the CCR5. Overall, the genotypic tropism testing on population-based V3 sequencing, is a valid tool for tropism determination in clinical practice. Indeed, all R5 Dinaciclib CDK inhibitor genotypically predicted viruses were responsive to maraviroc in vitro in primary cells. This methodology has low cost and short turnaround, and has been recently shown to adequately predict virological response to maraviroc in drug-naive patients of the MERIT Trial. Finally, to better discriminate the viral entry and viral replication, we found no main differences in PBMC and CD4 + T cells by comparing the total HIV DNA copies with the p24 production in presence or absence of maraviroc. Some HIV-1 isolates not replicating in CD4 + T cells, reached high levels of HIV DNA, suggesting a latency phase after HIV-1 entry. The establishment of a latent infection has been generally considered to be dependent on the cell type infected by HIV. Our finding confirms the existence of potential viral mechanisms regulating the entry into a latent phase in lymphocytes. This point deserves further investigation. In conclusion, this study underlies the existence of complexity and heterogeneity among the HIV-1 population in terms of viral tropism. Our results reinforce the concept that HIV-1 tropism is a phenomenon not only dependent on the coreceptor usage but also on the replication capacity in different cell types. The majority of isolates efficiently replicated in both PBMC and CD4+ T-cells, regardless of their tropism, while macrophages mainly sustained the replication of HIV-1 isolates with pure R5 tropism. Moreover, the CCR5-antagonist maraviroc was active in both PBMC and macrophages against phenotypically pure R5 viruses, all R5 predicted by genotypic test. This supports the concept of extending the use of CCR5-antagonists to a spectrum of patients potentially larger than only those infected with a pure- R5 virus. It is now widely accepted that both genetic and epigenetic alterations contribute to tumor initiation and progression. Epigenetic gene repression, particularly of tumor CT99021 suppressor genes, may occur via several reversible mechanisms, namely DNA methylation, histone deacetylation or a combination of both. Hypomethylating agents, such as 5-aza-29-deoxycytidine, or histone deacetylase inhibitors, such as depsipeptide, are being evaluated in cancer clinical trials. Such epigenetic-based therapies have in common their ability to alter gene expression that facilitates tumor growth arrest or apoptosis.