Hematopoietic cell transplantation and HIV cure: where we are and what next?

Highly active antiretroviral therapy (HAART) or combination antiretroviral therapy (cART) has been so effective that HIV infection has now been transformed from a deadly disease to a chronic infection. Nevertheless, such therapies do not eradicate the virus, which persists in reservoirs that are not yet fully understood.1,2Consequently, patients must continue lifelong therapy, which has adverse effects; furthermore, it is costly and therefore not sustainable for people living in the parts of the world hardest hit by the epidemic. Thus, current research is directed at discovering new strategies toward a cure for HIV, including transplantation of engineered hematopoietic stem/progenitor cells and T cells as well as naturally occurring hematopoietic stem/progenitor cells that give rise to progeny resistant to HIV.

The report of a single patient cured of HIV with hematopoietic stem cell (HSC) transplant has raised tremendous hope, excitement, and curiosity in the field. The patient had HIV infection and leukemia and was transplanted in Berlin in 2007 using HSCs from a donor whose cells lacked the functional CCR5 coreceptor required for HIV to infect cells. Following the transplant, his antiretroviral therapy was stopped and his blood and various biopsy specimens showed no detectable HIV,3,4suggesting that he might be cured. However, it is not certain how functional cure was achieved with the “Berlin” patient: it could be attributable to some combination of the transplant conditioning regimen, the anti–T-cell chemotherapy, graft-versus-host effect, and/or other factors in addition to the lack of a functional CCR5 coreceptor.5 In addition to the Berlin patient, there have been early-stage clinical studies of engineered human progenitor cells and T cells expressing anti-HIV moieties, including CCR5-inactivated T cells.6-15 These studies demonstrated the safety and feasibility of such therapies, but their efficacy is yet to be evaluated.