By Rowena Johnston, Ph.D.
When the scientific community learned in a 2009 article in The New England Journal of Medicine that a man known as “the Berlin patient” had been cured of HIV, the news ushered in a new era of HIV research, one underpinned by the knowledge that curing HIV is possible.
But a single person represents an anecdote, and many questions remained unanswered. What are the best ways to measure a vanishingly small amount of virus to confirm that none remains? What were the key elements of his treatment that led to the cure? And most importantly, could this case be replicated?
Co-Principal Investigators Drs. Javier Martinez-Picado (front right) and Annemarie Wensing (center right), pictured with ICISTEM members including Dr. Gero Hütter, “the Berlin patient’s” physician, and Dr. Maria Salgado. Also pictured are Dr. Rowena Johnston (front, second from right) and Dr. Jeffrey Laurence (back row, right) of amfAR.
amfAR addressed the first question by bringing together a team of researchers to intensively study the blood and tissues of Timothy Brown, the Berlin patient, who has been remarkably generous with his body and his time in the service of science. We also brought together another team of researchers to compare every available assay that could quantify low levels of persistent viral reservoir.
amfAR subsequently funded three separate teams to more closely interrogate the circumstances and procedures that led to Timothy Brown’s cure. One of those researchers, Dr. Timothy Henrich, followed the two so-called “Boston patients,” who, after unusually long delays, experienced viral rebound, confirming that their transplants did not cure their HIV infection.
The groundbreaking work conducted by amfAR’s ICISTEM consortium has been recognized by two prestigious awards. Dr. Maria Salgado, a researcher from the IrsiCaixa AIDS Research Institute in Barcelona, Spain, was presented with the inaugural Dominique Dormont Award during the International ADIS Society Conference on HIV Science in Paris in July 2017. And Dr. Jon Badiola of the Virgen de las Nieves University Hospital in Granada, Spain, was presented with a Best Young Abstract Award at the Annual Meeting of the European Society for Blood and Marrow Transplantation in March 2018.
As ever in science, even disappointing results are an opportunity to learn new facts. Scientific findings were increasingly suggesting that the genetic mutation in the donor stem cells that Timothy Brown received were a vital, perhaps even foundational, element of his cure. Another grantee, Dr. Jonah Sacha, concluded that the rejection reaction of the transplanted cells against the recipient’s immune system (known as graft versus host disease) plays a central role in success against cancer and probably also HIV.
In 2012, amfAR began discussions with a group of European researchers with the goal of establishing a research consortium, now known as ICISTEM (www.icistem.org), that could take these questions even further. We chose Europe because it has the highest proportion of people living with the CCR5-delta32 genetic mutation that appears to have been central to Timothy Brown’s cure. The consortium is co-led by the IrsiCaixa AIDS Research Institute in Barcelona, Spain, and the University Medical Center Utrecht in the Netherlands. It includes HIV cure researchers, cancer transplant doctors, and doctors working to register stem cell donors and test their cells for the genetic mutation.
In January, amfAR met with the ICISTEM team in Berlin for an annual progress update and planning session. They have so far enrolled more than 30 patients with cancer and HIV who have received or soon will receive stem cell transplants. And they have identified over two million potential stem cell donors with the CCR5-delta32 mutation.
Most exciting, the group has conducted exhaustive testing for persistent reservoir in many of the transplanted participants and in several cases are unable to find evidence that any HIV remains. They are preparing to embark on the next phase of this scientific journey, the definitive test of a cure, namely the withdrawal of antiretroviral therapy. Results will take at least a year, and while we cannot promise that any of these people will be shown to be cured, we can promise that amfAR is pursuing every promising avenue to discover what it will take to finally cure HIV.
Dr. Johnston is an amfAR Vice President and Director of Research.