DC are major targets of HIV-1 during the early events of infection. Yet, HIV-1 infects these cells only inefficiently in vitro as compared with CD4+T lymphocytes. Accordingly, we have previously identified a strong post-entry block to HIV-1 replication in MDDC as a result of the cellular restriction factor A3G. Furthermore, we have demonstrated that As₂O₃, a drug used to treat acute promyelocytic leukemia, can fully eliminate the potent post-entry restriction of HIV-1 infection in MDDC and in blood-derived MyDC by mechanisms that were unclear. We are now exploring the interplay between As₂O₃ and A3G-mediated restriction in primary DC subsets. Here, we report that As₂O₃ counteracts A3G-mediated restriction in MyDC but not in MDDC. RNAi of A3G in MyDC indicated that the As₂O₃-mediated increase of HIV-1 infection was largely dependent on the presence of the cellular restriction factor. This study reveals an unexpected interplay between As₂O₃ and A3G-mediated restriction to HIV-1 infection in primary human MyDC.