Bone marrow transplantation

Early in the epidemic, immune suppression followed by a bone marrow transplant from an HIV-negative donor was proposed as a possible way to get rid of HIV-infected CD4 cells; one American activist even tried a bone marrow transplant from a baboon. A few people with AIDS who received bone marrow transplants before the advent of highly active antiretroviral therapy (HAART) had undetectable HIV after the procedure, but eventually the virus came back.

In 2007, French researchers reported on an HIV-positive man who was taking HAART and had an undetectable blood viral load before receiving a bone marrow transplant. After the transplant, ultrasensitive tests did not find any HIV genetic material in more than a million tested cells. But after the man had to stop taking antiretroviral therapy due to drug toxicity, both his blood viral load and HIV proviral DNA in cells again became detectable.¹

However, in a case which rapidly made news headlines, an HIV-infected man in Berlin who discontinued ART following a bone marrow transplant has remained free of virus for 38 months according to the most sensitive tests available. The patient's own CD4 cells appear to have entirely disappeared, presumably due to the immunosuppressive therapy used, and have been replaced by cells produced from the donated bone marrow.²

The researchers who conducted the operation and follow-up have now pronounced the man cured of HIV infection, but the procedure used in this case is unlikely to be possible in many people due to the very gruelling course of chemotherapy, and the need for a CCR5-matched matched bone marrow transplant.³

Researchers do not yet fully understand the reasons for this outcome; many features of the case appear on investigation to offer only partial explanations. For instance, the marrow donor possessed a rare genetic variation (a homozygous CCR5-delta32 mutation) resulting in a complete absence of CCR5 co-receptors in the donor's immune cells (and hence the transplant recipient's "replacement" cells). Although the lack of CCR5 co-receptors protects these cells from infection by R5-tropic virus, it does not explain why they did not become infected with X4-tropic virus, to which they should still be susceptible and which had been identified in the recipient prior to the transplant.

Despite this and other unanswered questions, researchers are already beginning to explore how CCR5-deficient cells might be transferred to patients from donors or created by gene therapy techniques.