Clearance of apoptotic cells increases macrophage secretion of antiinflammatory mediators and might modulate viral replication in human immunodeficiency virus (HIV) type 1–infected macrophages. To study this, primary macrophages were infected with HIV-1 and exposed to apoptotic cells. It was found that phagocytosis of apoptotic cells potently enhanced HIV-1 growth. The peptide Arg-Gly-Asp-Ser, which binds to integrin receptors, inhibited the uptake of apoptotic cells and the subsequent enhancement of HIV-1 replication. Viral replication was preceded by increased secretion of transforming growth factor (TGF)–b1 and partially reverted by anti–TGF-b1 antibodies. Moreover, anti–TGF-b1 antibodies inhibited HIV-1 replication in macrophages not exposed to apoptotic cells. A positive correlation was observed between TGFb1 production and HIV-1 growth, and the addition of TGF-b1 amplified HIV-1 replication in macrophages from low TGF-b1 producers. The findings suggest that TGF-b1 favors HIV-1 replication in macrophages and that the clearance of apoptotic cells by HIV-1–infected macrophages contributes to persistent viremia in patients infected with HIV-1.