Stem cell transplantation in the context of HIV – how can we cure HIV infection?

Abstract

All HIV target cells are derived from hematopoietic stem cells. More than two decades ago, a hypothesis was postulated that a cure for HIV may be possible by performing a transplant with HIV-resistant hematopoietic stem cells that would allow for an HIV-resistant immune system to arise. HIV-resistant stem cells could be generated by genetically modifying them with gene therapy vectors transferring anti-HIV genes. First attempts of stem cell gene therapy for HIV were carried out in the USA in the 1990s demonstrating safety, but also little efficacy at that time. The first demonstration that the postulated hypothesis was correct was the cure of an HIV-infected individual in Berlin in 2009 who received an allogeneic bone marrow transplant from a donor who lacked the CCR5 chemokine receptor, a naturally arising mutation rendering HIV target cells resistant to infection with macrophage tropic strains of HIV. In 2013, reports were published about a possible cure of HIV-infected individuals who received allogeneic bone marrow transplants with cells not resistant to HIV. We will review these stem cell transplant procedures and discuss their utility to provide a cure for HIV infection, including efficacious future stem cell gene therapy applications.

Keywords::

• allogeneic bone marrow transplantation for HIV
• anti-HIV genes
• bone marrow transplantation
• CCR5 receptor
• functional cure for HIV
• HIV
• HIV cure
• stem cell gene therapy for HIV

Financial & competing interests disclosure

The authors received institutional funds from University of California Davis (USA). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Target cells for HIV are derived from bone marrow stem cells.

• Bone marrow transplantation with HIV-resistant stem cells could potentially cure HIV infection by replacing a patient’s immune system with HIV-resistant immune cells.

• Stem cell gene therapy for HIV could produce an HIV-resistant immune system, but has been plagued with low clinical efficacy.

• The first cure of an HIV-infected individual was achieved by allogeneic bone marrow transplantation with hematopoietic stem cells from a donor with a CCR5 receptor deletion.

• Two more cases of a potential cure of HIV infection were reported after transplantation with allogeneic bone marrow stem cells not resistant to HIV.

• A functional cure for HIV is an achievable possibility.

• Possibly, more than one mechanism may be responsible for a functional cure for HIV after bone marrow stem cell transplantation.

• Future stem cell gene therapy for HIV approaches may be able to mimic the outcome of the first cure in a patient who received bone marrow stem cells from a donor with a CCR5 receptor deletion.