Back-burning to cure HIV: temporary depletion of all CD4+ cells and elimination of the extracellular reservoir with HIV immunotoxin therapy.

Temporary elimination of all host cells for the human immunodeficiency virus (HIV) combined with dislodging HIV from its extracellular reservoir could cure acquired immunodeficiency syndrome (AIDS). This combination would be effective because the virus is dependent on host cell integration or on the membrane protection of B cells or of follicular dendritic cells (FDCs) for its survival and because the CD4(+) host cells are leukocytes that are naturally renewable through hematopoiesis. By treating HIV patients with a combination of humanized antibodies it should be possible to achieve both goals. To deplete HIV host cells, a humanized antibody against CD4 should be fused to an apoptosis-inducing toxin; and to void the extracellular reservoir, a fragment of a humanized antibody against CD21 should be used. Because only CD4(+) cells would be destroyed, hematopoietic stem cells would be spared, and would spontaneously replace the depleted cells. We call this hypothetical new HIV treatment "HIV Immunotoxin Therapy (HIT)". Once the HIV viral load reaches zero, the HIT would be withdrawn and IL-2 or luteinizing hormone releasing hormone analogues (LHRH-A) might be administered to accelerate the natural replacement of the CD4(+) T(H) cells and macrophages. Killing all HIV host cells may seem counterintuitive at first, because it requires the purposeful destruction of the very cells that we ultimately hope to preserve for AIDS patients, but just as controlled back-burning purposefully creates a trap to stop a wildfire from burning out of control, this method could provide a mechanism to extinguish HIV.