A novel approach to HIV therapy: highly active antiretroviral therapy and autologous hematopoietic cell transplantation

Abstract

Highly active antiretroviral therapy dramatically decreases in vivo viral replication to levels below the level of clinical detection, but does not eradicate HIV-1 infection on the basis of persistent low-level or cryptic viral replication and latent provirus in resting CD4+ T lymphocytes. Immune activation therapy has begun to be used in attempts to increase the turnover rate of the latent virus reservoir through activation of infected cells that comprise this reservoir, in order to promote cell death and accelerate virus clearance. Recent reports have not demonstrated complete virus ablation. Autologous hematopoietic cell transplantation now appears as a safe, feasible, and reasonable approach for Aids-related lymphoma in patients who meet criteria for transplantation. The hypothesis is based on the possibility that hematopoietic stem cells from a HIV-positive patient could be collected before the patient becomes infected with HIV. Then, the proposed treatment consists of the following assumptions. HAART keeps viral replication below the level of detection, limiting the infection to latent provirus in resting CD4+ T lymphocytes. It is presumed here that myeloablative conditioning regimen can lead to the killing of all the cells that, in theory, harbour the virus. The following transplantation of the autologous hematopoietic stem cells, collected before HIV infection, would allow the complete recovery. The hypothesis is to be tested on a suitable animal model. After the collection of hematopoietic stem cells, the animal is experimentally infected with the immunodeficiency virus. HAART is given after plasma viral RNA becomes detectable. By myeloablative conditioning regimen all the cells harbouring the virus are supposed to be killed. Then, as the viral load is kept undetectable by HAART, the animal undergoes autologous hematopoietic stem cell transplantation. Antiretroviral therapy is interrupted a month after engraftment has taken place. Although hematopoietic stem cells from man before infection with HIV are unlikely to be available, a successful test on the animal would suggest a new approach which could allow the cure of HIV in future.