麻豆传媒

Almost 3 years after the underwent a hematopoietic stem cell transplant and stopped taking antiretroviral treatments for HIV infection, he remains in remission and intends to "be an ambassador of hope" to millions of other HIV patients.

In a roundtable discussion with scientists and the media at the virtual meeting of the 2020 International AIDS Society, Adam Castillejo, 40, 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 another disease, the coronavirus COVID-19 pandemic, Castillejo said that he more than most people understands 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 – the first individual apparently cured of HIV through a similar therapy -- may soon be joined by several other patients, said Ravi Gupta, MD, of the University of Cambridge in England, who headed Castillejo's treatment team.

"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 five other transplants with the Delta-32 mutation," 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."

In the roundtable, Gupta outlined the history of Castillejo, who was diagnosed with HIV infection in 2003 and then diagnosed with Hodgkin's lymphoma 10 years later. Chemotherapy and an autologous stem cell transplant were unsuccessful.

"The next procedure is to receive a bone marrow treatment from someone who is unrelated but matched by tissue," Gupta said. Learning from treatment used for the Berlin patient, Gupta's team sought "a donor who had a particular mutation called the Delta-32 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 uses two proteins as cell entry portals and one of them is CCR5."

Castillejo "had the transplant in May 2016, and we watched him with numerous blood tests over the next year and a half," Gupta continued. "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."

Since then, Gupta said, "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."

"We talk about the London and Berlin patients, and of course, this is hugely important for them," commented Mark Dybul, MD, of Georgetown University in Washington, D.C., "but as has been pointed out, we cannot do allogeneic transplants on a large scale. It's not safe to do them because it has a very high mortality and morbidity rate."

Still, he added, "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," Sharon Lewin, MBBS, PhD, of the University of Melbourne, and co-chair of the International AIDS Society Initiative Towards an HIV Cure that 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."

Said Dybul, "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. 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."

Gupta said emerging genetic manipulation approaches 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," 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.

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