The patients described in this abstract were on antiretrovirals at the time of the reduced-intensity conditioning allogeneic hematopoetic stem cell transplantation 4.3 years ago and remained on their ART until 15 and 8 weeks ago, respectively, at time of presentation at IAS 2013. The researchers looked diligently for HIV-1 DNA or replication competent proviruses in peripheral blood mononuclear cells and rectal tissue. None was found.
These findings are complex but offer great insight into the future of HIV research in this area. Stem cell transplantation is not a viable option for all HIV-positive patients due to the high morbidity and mortality rates associated with this treatment. However, this research shows that is possible to eradicate the HIV reservoir. This notion was previously unclear. These findings build upon the results of Timothy Ray Brown, also known as “The Berlin Patient,” Mr. Brown needed a stem cell transplant to treat his acute myeloid leukemia. He was given stem cells from a donor, who was a CCR5 delta 32 homozygote. The donor was intentionally chosen with the hope that Mr. Brown’s new T cells would be resistant to HIV infection. It has been more than 5 years since Mr. Brown’s transplant and he remains free of HIV replication. CCR5 is a co-receptor used by most strains of HIV, along with CD4, to enter T cells. Physicians and scientists thought the reason that HIV did not “come back” was that Mr. Brown’s new T-cells (those derived from donor stem cells) were resistant to infection with HIV.
The patients presented by Drs. Henrich and Kuritzkes received cells from wild-type CCR5 donors. Their new T-cells are not resistant to HIV infection. The patients were conditioned with chemo and radiation therapy. This conditioning destroys the native bone marrow and lymphocytes. After conditioning, each patient was given stem cells from a “normal” donor and each was maintained on their HIV medications. After a period of years in which no evidence of HIV infection could be found, the HIV medications were stopped. Months later, there is no sign of HIV replication in either patient. These data suggest that the reservoir or “pool” of latently infected cells can be destroyed completely. In Mr. Brown’s scenario, it was assumed that the “pool” was not and could not be destroyed and that the new T cells, resistant to HIV infection, were essential to his “cure.” These new data contradict that theory and support the hypothesis that the “pool” can be eliminated and a “cure” can be mediated through this process alone.
These findings give hope to the prospects for cure of all HIV patients. One can imagine a future therapy, much more benign than the conditioning associated with stem cell transplantation, that could eliminate the “pool” and “cure” the patient. Perhaps a form of mild autologous stem cell transplantation might be designed, which has minimal side effects. Currently, it is difficult to envision how any therapy, which involves the elimination of a patient’s existing T cells, could be as benign as today’s HIV medication regimens.
Erin Murphy Santos, PA-C, MPH, and Stephen M. Smith, MD
Smith Center for Infectious Diseases and Urban Health
East Orange, Newark
Disclosures: Santos and Smith report no relevant financial disclosures.