In summary, these studies demonstrate a proof of concept that peptides from gp41 HR2 can be delivered to the precise sites of HIV-1 entry when conjugated to chemokine receptors CCR5 or CXCR4, with C34-conjugated CXCR4 conferring particularly potent, broad and durable protection from HIV-1 infection to primary CD4+ T cells in vitro and in humanized mice. The gene discussed is CXCR4; the disease is HIV-1 infection.