The Issue of Tissue: Getting to the Source of the HIV Reservoir

Not all stem cell transplants in individuals living with HIV and cancer, such as those used to cure Timothy Ray Brown and Adam Castillejo, among others, have been successful. Yet much can be learned about curing HIV from those whose lives could not be saved.

Research question
Currently the only curative intervention for HIV is to transplant donor cells with a CCR5 delta32 genetic mutation in a person living with HIV (PLWH). But the impact of such transplants on HIV reservoirs in various organs has not been extensively characterized. A consortium of European researchers known as IciStem, established through amfAR funding, sought to gauge this impact by studying autopsy specimens from two individuals who underwent such transplants but were not cured and died soon afterwards.

Findings
The first individual had been infected with HIV for 14 years and treated with antiretroviral therapy (ART) for that entire period. He was given a transplant in an attempt to cure a blood disorder known as MDS. On the 36^th day following that procedure he achieved 100% chimerism. That meant that all his newly formed immune and other blood cells were the offspring of the donor and should be resistant to HIV infection. However, 29 days later that 100% value fell to 85%—presumably related to an initially undetected population of recipient cells that were not destroyed by the transplant preparation procedure. He died of severe sepsis. At that time his blood still had no evidence of HIV, but all organs sampled, from brain to lymph node, showed signs of persistent infection.

The second individual had been infected with HIV for 22 years and treated with ART for the last 19 years. He required two transplants in an attempt to cure his acute leukemia—the first one having failed to take hold—and on the 100^th day following the first transplant (29 days after the second procedure) he achieved 100% chimerism. However, he died of lung failure eight days later. At that time no virus could be found in the blood, but the lymph node and spleen showed persistence of an HIV reservoir.

Impact
The authors emphasize the need for examining tissues, not just blood, of PLWH having undergone potentially curative interventions as their results document that “[t]issues play an essential role as a long-standing viral reservoir and routine [blood] sampling in living HIV-1-individuals will be insufficient to represent the extent of this reservoir.”

amfAR’s role
amfAR was a funder of this research.

Original article
http://www.ncbi.nlm.nih.gov/pubmed/36146874

Dr. Laurence is amfAR’s senior scientific consultant.