Mr. Susman is a freelance medical writer based in Florida, USA. He travels worldwide to report from medical conferences, writing regularly for wire services, internet websites, and medical journals such as the Journal of the National Cancer Institute and AIDS.
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Vaccines have proven ineffective, various treatment therapies have not worked, and intermittent treatment schemes have been failures in the worldwide treatment of human immunodeficiency virus (HIV) – the pathogen that causes AIDS.
But there are 2 individuals in the world who through unique treatments for blood cancer have also been able to defeat HIV infection as well.
At the virtual International AIDS Conference, forced to go online due to the COVID19 pandemic instead of meeting in San Francisco, the so-called ‘London Patient’ said that his functional cure of HIV should show the world that there really is hope that HIV can be defeated.
Almost 3 years after Adam Castillejo, 40, stopped taking antiretroviral treatments, his HIV infection remains in remission, and gives him, as he says, a chance to live disease-free and “be an ambassador of hope” to the millions of people.
In a roundtable discussion with scientists and the media, Castillejo, said, “I am very humble to be the second person who had been cured of this disease. Sometimes fear can overwhelm you, but don’t give up on hope. Sometimes things can look so overwhelming for you, so desperate, so powerless. But have faith; have hope. Things can change.”
Even in today’s world that is dominated by COVID19, Castillejo said that he more than most people understand how the pandemic affects the population. “I had to be isolated for long periods due to my bone marrow transplant therapy. I had to wear a mask. I think many people can now appreciate what I have been living with for many years, staying at home, not going out, no interactions with people, avoiding public places, avoiding public transport, practicing social distancing. It has opened a lot of people to my world, but don’t give up on hope,” Castillejo said.
Castillejo and Timothy Brown, the so-called Berlin patient – the first known cure of HIV who went through a similar therapy, may soon be joined by several other patients, said Ravi Gupta, MD, professor of clinical microbiology and Wellcome Trust senior fellow in clinical science at the University of Cambridge, United Kingdom, and the head of the team that treated Castillejo.
“At the moment we haven’t, at our center, been pursuing any further cases, but there is a very large European consortium and they have carried out something like 5 other transplants with the Delta32 mutation,” Dr. Gupta reported. “We know that one of those individuals has been in remission after stopping antiretrovirals, and as of last year had been off treatment for 7 months without any rebound. Up to date, I haven’t heard that any of the other patients have yet interrupted antiretrovirals.”
At the virtual roundtable, Dr. Gupta outlined the history of Castillejo who was diagnosed with HIV infection in 2003. “He subsequently developed Hodgkin’s lymphoma 10 years later, and importantly. he was not put on antiretrovirals because his CD4 counts were in the range where treatment wasn’t offered in those days,” he said.
“In 2013, Castillejo was diagnosed with Hodgkin’s lymphoma, and unfortunately, multiple lines of chemotherapy that are standard practice, were not successful, and usually the next step after drug treatment is an autologous transplant, but that, also, was not successful,” Gupta said.
“The next procedure is to receive a bone marrow treatment from someone who is unrelated but matched by tissue,” he said. Learning from treatment used for the Berlin Patient, the London team sought “a donor who had a particular mutation called the Delta32 mutation in a gene called CCR5, a gene that codes for a protein that we have on our white blood cells and is absolutely essential for HIV to enter cells and cause infection. HIV needs 2 proteins to get into cells and one of them is CCR5.
“Our aim was to replicate the Berlin Patient whose treatment had been described back in 2009,” Dr. Gupta said. “The London Patient had the transplant in May 2016, and we watched him with numerous blood tests over the next year and a half. The blood tests showed the virus was below detection limits while he was on antiretrovirals, and then we interrupted his treatment 16 months after transplant in September 2017.
“We monitored blood closely and frequently and we saw no evidence of the virus coming back, which was remarkable, and, at the time, very exciting. We reported the findings after 18 months and again after 30 months to March 2020, and there is still no rebound in the blood.
“We sampled various tissues in the gut and axilla that showed no evidence of virus that could make copies of itself but we did see these, what we call, fossils of HIV. Although there was no rebound, we did see evidence that there had been virus. Remission had remained thus far,” Dr. Gupta said.
While remarkable, Mark Dybul, MD, co-director for the Center for Global Health Practice and Impact and professor of medicine at Georgetown University, Washington, DC, and director of the HIV Cure Africa Acceleration Partnership, said, “We talk about the London and Berlin patients, and of course, this is hugely important for them, but as has been pointed out, we cannot do allogeneic transplants on large scale.
“It’s not safe to do them because it has a very high mortality and morbidity rate,” Dr. Dybul said, “but the important thing is: Cure is no longer theoretical. We know it is possible. Now we have to learn how to move from this absolutely remarkable achievement and move it into people. Now we have to make it accessible to all.”
“We are looking for a one-shot cure, but we are many, many years away from that,” said Sharon Lewin, MBBS, PhD, professor of medicine at the University of Melbourne, and the co-chair of the International AIDS Society Initiative Towards an HIV Cure which sponsored the roundtable.
“We have to try to mimic what these patients have received through gene therapy so it can become simpler and easier,” she said. “The cure must be inexpensive, scalable and highly effective.” She noted that the procedures that resulted in the cure of both the Berlin Patient and the London Patient fall short of those requirements. It is expensive – requiring bone marrow transplantation from selected donors, and it unlikely to be available to even a small percentage of people living with HIV who are surviving on lifelong antiretroviral therapy.
In addition, she noted, “We aren’t going to be using the allogeneic bone marrow transplant such as used in Adam’s case unless they also have an associated blood cancer.”
But Dr. Dybul said, “It is important that we focus on cure for a variety of reasons. A couple of years ago, it seemed like a fantasy, but science is advancing and we have a tremendous opportunity, and now is the time to engage.
“I think for many of us, COVID and the impact of COVID, especially in resource limited settings on access to antiretroviral therapy has highlighted the need for cure. We won’t be able to predict disruptions in treatment and other services in the future,” he said. “You have seen the reports and data that if this continues, we could roll back HIV advances in Africa by 20 years within the next couple of years because people aren’t going to clinics and the lockdowns are causing significant problems with access to services, up to 70% declines in some places. It is just an example of the need for this.”
Dr. Gupta suggested that there are methods using genetic engineering that could open the door to more people living with HIV. “The field of genetic engineering is not new, but technology has been refined over time. Gene therapy vectors are now much safer, and now HIV is on the menu of diseases that we want to treat with this technology.
“There are a number of different ways of doing modification of DNA and genes now, but the issue has been the number of cells that you can actually modify, and really for this to work you have to take cells from the patient; modify virtually all of them, and then put them back in the patient. Even if you can do that, there are still cells in the body that haven’t been modified.
“So we are making small steps to reaching the final goal which is to modify all the susceptible cell targets in the body in a safe way. We really are in the early stages of this. We are on the road, but it is a long way,” Dr. Gupta said.
“Don’t give up on hope,” Castillejo appealed. “People are working hard to find a more feasible and practical way to cure everyone. My cure is very challenging, very complicated, and very difficult to replicate, but I am living proof that it is possible.”
He admitted that his journey has been fraught with dark places. “It was a very dark period for me when I realized my mortality,” Castillejo said. “It was a very challenging period for me. I tried to take control of my illness. In my case, I thought, ‘Well, I have tried the best I can. My doctors have tried the best they can for me.’ And then I had the opportunity to be cured of my cancer and then of my HIV: it was like a 360-degree change.
“I had to go through a difficult path,” he said. “You know, you realize you are in the final stages of your life, you know you are going to go, and you are going to die. And then a few months later to be told you can be cured of your HIV and be cured of your cancer, I had to regain the passion for life.
“I am very fortunate to have been in the right place at the right time and to have the right medical team at that time,” he said.