HIV-1 efficiently entered RBCs that co-expressed CD4 and CCR5, but viral entry was not required for neutralization, as CD4 or CD4-GpA expression in the absence of CCR5 was sufficient to potently neutralize HIV-1 and prevent infection of CD4+ T cells in vitro due to the formation of high-avidity interactions with trimeric HIV-1 Env spikes on virions. The gene discussed is CD4; the disease is infection.