Graft versus host and auto-immune reactions may explain the discontinuity and severity of HIV1-AIDS disease

Abstract

Despite recent use of potent antiretroviral drugs, the goal of eradication of human immunodeficiency virus (HIV) and restitution of the immune system has not been achieved. The present work reviews the literature on syngeneic or allogeneic bone marrow transplantation (BMT) in patients infected with HIV and in patients with acquired immune deficiency syndrome (AIDS). Thirty-two such attempts have been reported between 1982 and 1996. In two cases, HIV was eradicated and previously positive polymerase chain reaction (PCR) for viral DNA and RNA became negative. One patient had transient disappearance of HIV by PCR and several more, including one who underwent xenotransplantation of baboon bone marrow, experienced clinical and laboratory improvement. These results correlate with use of intensive pre-transplant cytoablative conditioning with chemotherapy and radiotherapy. Curative mechanisms of conditioning include elimination of several cell populations: infected cells, cells susceptible to infection, uninfected chronically activated cells responsible for autoimmune phenomena, and exhausted haemopoietic and lymphopoietic progenitors. They are repopulated by donor-derived cells that could mount a successful antiviral response through cytotoxic T lymphocytes. Non-specific graft-versus-host effect of allogeneic bone marrow would also help eliminate residual reservoirs of virus, especially macrophages. Protection of repopulating cells from infection could be achieved by a combination of antiretroviral agents and gene therapy strategies may be of additional benefit.