Maraviroc is a recently Food and Drug Administration approved antiretroviral drug with a novel mechanism of action. It can be used for the treatment of HIV drug-na?��ve and drug-experienced patients, and also very important, of patients with multi-resistant viruses to other antiretroviral drugs. It acts by binding to the CCR5 coreceptor within a cavity located among the ARRY-142886 membrane-spanning helices, and it stabilizes the receptor in a conformation not efficiently recognized by the viral gp120, thus preventing HIV-1 entry. Based on this specific mechanism of action, maraviroc is recommended only in patients infected by pure R5 viruses. So far, very few studies have focused on the in vitro and in vivo efficacy of maraviroc ALK5 Inhibitor II against HIV-1 dual-tropic viruses. Similarly, very few studies also analyzed the replication capacity of HIV-1 dual-tropic viruses in human primary cells, such as CD4+ T-cells and macrophages, that are the two principal targets and sanctuaries of HIV infection. Indeed, macrophages can sustain viral infection for long periods of time, from weeks to months, in vitro and in vivo and they can efficiently transfer virus to CD4+ T-lymphocytes contributing to their depletion in human cellular compartments. It was recently recognized that R5 HIV-1 isolates can markedly vary in their replication capacity in macrophages and that some X4 viruses are also capable of replication in these cells. For all of these reasons, the innovative aim of the study was to analyze both the replication capacity and the in vitro efficacy of maraviroc against clinical isolates with different tropic characteristics in human primary macrophages, peripheral blood mononuclear cells and lymphocytes. In particular, we tested the activity of entry antagonists against several dual-tropic viruses with a wide range of phenotypic and genotypic tropic preferences. This work shows that HIV-1 clinical isolates exhibit a wide range of viral tropism and different rates of replication, and highlights the ability of maraviroc to inhibit not only pure-R5 but also dual/mixed-tropic viruses in human primary cells. These results underline the complexity and the heterogeneity of the viral population circulating in HIV-1 infected individuals, suggesting that using clinical isolates is a good model to appreciate the real viral contribution in mechanisms underlying HIV-1 pathogenesis in vivo. We found that the majority of HIV-1 isolates efficiently replicated in PBMC and T cells. A weak correlation was observed between the efficiency of replication and viral tropism in both these cell types. In contrast, a stronger and significant correlation was observed in MDM. Consistent with higher expression of CCR5 co-receptor on their membrane, macrophages mainly sustained the replication of HIV-1 isolates with pure tropism. On the other hand, the replication of all dual/mixedtropic viruses with a genotypic FPR,20% was very poor in these cells.