Stem Cell Transplant Found to Lower HIV Reservoir

Used correctly, antiretroviral therapy is an effective tool that reduces viral load in people living with HIV, allowing them to live normal or near-normal lifespans. Some can even safely conceive and birth children without fear of transmission. However, antiretroviral therapy has never been able to completely eradicate the virus because of a latent reservoir of HIV that remains in every patient. Now, a team of investigators based in Barcelona, Spain, have found that graft vs host disease may enable diminishment of the HIV reservoir, putting researchers on the path to finding a cure for HIV.

Only 1 person with HIV has ever experienced a complete “cure.” The so-called Berlin patient, as he is known in medical literature, is completely free of HIV after being diagnosed with leukemia and undergoing 2 stem-cell transplants from the same donor more than a decade ago. Other people infected with HIV who have had stem-cell transplants have not been able to achieve complete eradication of the virus, although there are signs that these procedures can act to greatly lower the levels of HIV reservoir residing in the body.

A team of investigators based in Barcelona conducted a study of 6 male participants in the IciStem project, which is funded by amfAR, the global organization dedicated to ending HIV and AIDS. This project closely followed people with HIV who were taking antiretroviral therapy and who also needed stem-cell transplants due to hematologic diseases such as leukemia. After undergoing stem-cell transplants, 5 of the 6 patients had undetectable viral reservoirs. One of them no longer had any HIV antibodies in his blood.

The aim of the study was to determine what factors might be involved in the significant reduction of these HIV reservoirs as a pathway to the ability to completely eradicate HIV from the body. The scientists discovered that immune-compatible donors who have a particular gene mutation known as CCR5 are an important factor, although such donors are relatively rare. As such, they kept looking for other variables.

The team discovered that one possibility behind the lowering of the HIV reservoir is graft vs host disease. Graft vs host disease is a common complication of stem-cell transplants that occurs when the new donor immune cells attack certain cells in the host, or recipient. Although graft vs host disease necessitates immune-suppression medication and has a significant mortality rate, for people with HIV who survive the transplant and its aftermath, graft vs host disease may enable diminishment of the HIV reservoir.

“We believe this reactivity [between donor cells and host cells] might eventually help to sweep away any leftover infected cell[s] from the recipient that might still be circulating in the body, thus contributing to the clearance of the viral reservoir,” Javier Martinez-Picado, PhD, a research professor at the IrsiCaixa AIDS Research Institute in Barcelona and an author of the study, said in an interview with Contagion®. Four out of the 5 patients in this study who were found to have undetectable HIV reservoirs posttransplant had developed grant vs host disease during recovery.

This study reveals that the type of donor may make a difference in whether the recipient clears his or her reservoir of HIV. One of the 6 subjects received cord blood cells instead of adult donor cells; that subject did not experience graft vs host disease and was subsequently found to have a detectable HIV reservoir after transplantation. The authors posit that the cord blood cells being a “less mature graft source...may have moderated the potential graft-versus-HIV-reservoir effect,” they wrote in their report.

Another factor could be the time it takes to achieve full chimerism, or for all of the donor cells to be present in the host. Based on the results of this study, a prolonged period to achieve full chimerism may be problematic. The single participant who did not see a full eradication of his HIV reservoir took more than a year to achieve full chimerism, in contrast to the other subjects, 1 of whom achieved full chimerism within a month of the transplant.

A third possible factor in the eradication of the HIV reservoir is pre-transplant conditioning.

“Pre-transplant conditioning [such as] chemotherapy and sometimes radiotherapy...helps to reduce the viral reservoir, as it eliminates recipient hematological cells which will be replaced by the new cells from the donor—although some studies show that the influence of conditioning in the viral outcome after transplant is limited,” Dr. Martinez-Picado said.

Because stem-cell transplants are complex, they are not recommended as a way for a person living with HIV to try to rid himself of the disease.

“This is a high-risk medical procedure,” Dr. Martinez-Picardo explained. “At the moment, this strategy is not scalable, but it allows researchers to understand more about viral reservoirs, and how and where to look for latent viruses. In addition, alternative more scalable interventions are being investigated.”

Contagion® HIV Editor, Jason Schafer, PharmD, MPH, an associate professor at Jefferson College of Pharmacy in Philadelphia, who was not involved with this study, agreed that getting rid of cancer, not HIV, is the primary reason for a stem-cell transplant.

“Investigations such as these do, however, provide insight into potential therapeutic strategies with the aim of reducing [or] eliminating the HIV reservoir aside from transplantation,” he told Contagion®.

Ms. Saloman is a health writer with more than 20 years of experience working for both consumer- and physician-focused publications. She is a graduate of Brandeis University and the Medill School of Journalism at Northwestern University. She lives in New Jersey with her family.