By Ben Burwitz, Ph.D., PQ Monthly
In June, two physicians at Harvard medical school reported on a pair of HIV+ patients who no longer had detectable HIV in their blood following discontinuation of their antiretroviral drug therapy. The finding was published in the Journal of Infectious Diseases and believed to be a significant step forward in the search for an HIV functional cure. However, the mechanisms that contributed to this unprecedented viral clearance were then, and remain now, entirely ambiguous.
What we do know is that both patients also suffered from lymphoma and received a therapeutic stem cell transplant, a risky procedure, but one that has shown promise as a last resort against cancers of the blood and lymphatic system. Stem cell transplantation is preceded by chemotherapy and radiation, which destroy the recipient’s immune system, paving the way for the donor stem cells to divide, mature, and reconstitute the depleted immune cells. As the donor cells expand, they kill remaining recipient immune cells that avoided elimination by chemotherapy and radiation, a phenomenon known as graft-versus-host disease. The doctors at Harvard have speculated that graft-versus-host disease may be an important mechanism by which the patients’ remaining HIV+ infected immune cells are cleared by the donor derived immune cells, but much more research will be required to determine the processes governing the unexpected HIV clearance from the blood.
It was recently reported on December 6 that HIV has re-emerged in both patients, following months of undetectable HIV in the blood. Many saw this as a huge blow to HIV cure research. However, the extravagant headlines that this is a decisive blow to HIV cure research are unfounded. Dr. Timothy Henrich eloquently summarized the study in an interview with CNN:
“The return of detectable levels of HIV in our patients is disappointing, but scientifically significant. We have demonstrated HIV can be reduced to undetectable levels by very sensitive research assays and the virus persists. Our results also show that the immune system can play a major role in reducing the viral reservoir, but may not be able to do the job alone. It is likely that a combination of drugs and immune therapies that target the reservoir will be needed to establish long-term remission of HIV infection.”
Indeed, while we all hoped this was the silver bullet against HIV, we must remember that not all is lost. We take away knowledge on the HIV reservoir that directs future research into how best to eradicate the final sources of virus, and that is good news. The other good news? Both patients are back on antiretroviral drugs and are responding well to their therapy.
Ben Burwitz is an HIV researcher at Oregon Health and Science University. He received his Bachelors of Science in molecular biology in 2004 and his Doctor of Philosophy in cellular and molecular pathology in 2010, both from the University of Wisconsin.