CD4 and infection: While in vitro studies have reported that vpr is necessary for infection of macrophage, but not CD4+ T cells [24-26], our observation of defects in vpr in M-tropic lineages in the blood before ART (i.e. in replicating virus) and during ART (i.e. virus being produced from infected macrophage without replication) provides strong evidence that loss of Vpr function impacts both virus replication and expression in macrophage.