As a useful alternative to employing soluble CD4 to inhibit binding of human immunodeficiency virus type 1 (HIV-1) to target cells, the introduction of CD4-bearing erythrocyte has been proposed by two study groups (see Refs. (5,6)). Prominently, Nicolau and colleagues demonstrated that the electroinserted CD4 molecules in the membranes of erythrocytes are capable of mediating HIV-1 entry. The implications of the studies are that inactivation of the integration-dependent retrovirus by the facilitation of entry into the nucleus-free cells, referred to as 'fake host trap' or 'host cell decoy', may be a possible therapeutic approach. Here we expand this concept to include genetic modification of autologous hematopoietic stem cells and review the relevant theoretical basis. Effective application of molecular technologies to induce partial replacement of hematopoiesis may be critical for this strategy.

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