03/08/2019

A Second HIV-Positive Patient May Have Been Cured. Now What?

11:56 minutes

Nearly 12 years ago, a cancer patient infected with HIV received two bone marrow transplants to wipe out his leukemia. After nearly dying multiple times, the patient, Timothy Ray Brown, recovered and was cancer-free. But later, his doctors discovered his HIV had also disappeared, thanks to a mutation in the donor cells that made them resistant to HIV infection.

Brown has been off anti-retroviral medications for more than a decade, and HIV researchers have been trying to replicate Brown’s cure ever since.

Now, researchers in the U.K. reported in Nature earlier this week that their patient, a man known only as “the London patient,” had been in remission and off anti-retroviral therapy for 18 months after undergoing a similar bone marrow transplant, with the same gene mutation involved, to treat leukemia. While the team is hesitant to call their patient cured, he is the first adult since Brown to remain in remission for more than a year after stopping medication.

But what do these two patients’ recoveries, requiring risky and painful transplants, mean for the millions of others with HIV around the world? Two HIV researchers not involved in this research, Katharine Bar of the University of Pennsylvania and Paula Cannon of the University of Southern California, talk to Ira Flatow about the latest treatments that could someday be more broadly accessible, including gene therapies and immunotherapy, and what hurdles clinical studies still face.


More On HIV Treatments

  • Read the full HIV-1 remission study published in Nature on Monday, March 5, 2019.
  • Read science journalist Apoorva Mandavilli’s reporting on the recent study and the London HIV-positive patient in the New York Times.
  • Find out about a third patient reportedly HIV-free after a bone marrow transplant reported March 5, 2019 in New Scientist. 
  • Read a personal reflection written by Timothy Ray Brown, the first HIV-positive patient to be cured, published in 2015.
  • Learn about past unsuccessful HIV treatments that involved bone marrow transplants, published in 2013 in Nature.
  • Learn more about global HIV and AIDS statistics from UNAIDS 2017 data, and NIH’s 2018 strategies for HIV treatments.

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Segment Guests

Paula Cannon

Paula Cannon is a Distinguished Professor of Molecular Microbiology and Immunology in the Keck School of Medicine at the University of Southern California in Los Angeles, California.

Katharine Bar

Katharine Bar is an Assistant Professor of Medicine at the Penn Center for AIDS Research, part of the Perelman School of Medicine, University of Pennsylvania in Philadelphia, Pennsylvania.

Segment Transcript

IRA FLATOW: This is Science Friday. I’m Ira Flatow. Later in the hour, unlocking the mysteries of our skeletons. But first, hopeful news this week for people living with HIV. A couple of drug trials have shown that a monthly long-acting injection is as effective as daily dosing of pills in keeping HIV in check. This news comes just days after researchers reported that a second man has been cured of infection from HIV, a man known only as the London patient. This comes 12 years after the cure of the world’s first person. 

Now why? Why a cure for these two? Well, both men, in addition to HIV, had cancer, requiring bone marrow transplants. And both received transplants of cells with one very particular genetic twist– HIV resistance. If the London patient remains off drugs and HIV-free, as he has for 18 months, then that would make two people in the whole world who have been cured of the virus, and only after risky procedures meant to save them from advanced cancer. 

So what does research hold for the other 37 million people hoping to live the best lives they can with a virus that was once a death sentence? Here to talk about the future of HIV research are two HIV researchers working on different kinds of treatments. Dr. Paula Cannon is Professor of Molecular Microbiology and Immunology at the Keck School of Medicine, University of Southern California in Los Angeles. Welcome Dr. Cannon. 

PAULA CANNON: Hello, Ira. Hi. 

IRA FLATOW: Nice to have you. Dr. Katharine Bar, Assistant Professor of Medicine in the Infectious Disease Division, University of Pennsylvania in Philadelphia. Welcome, Dr. Bar. 

KATHARINE BAR: Hello, nice to be here. 

IRA FLATOW: You’re welcome. Thanks for joining us. Dr. Cannon, as I just said, this patient’s cure required that you have a bone marrow transplant from a donor who happened to have this rare genetic mutation that makes people resistant to HIV infection. He is, as I say, now the second person to ever achieve remission for more than a year. There may be another patient in Dusseldorf, right, on the way to the same thing. 

PAULA CANNON: We’re hearing that, yeah. 

IRA FLATOW: But is this a practical cure for the other 37 million people? 

PAULA CANNON: No, not at all. But that doesn’t mean this is not incredibly exciting and of great value. And what researchers are focused on doing now is saying, can we understand why this very specialized and boutique treatment worked for these patients? And can we recapitulate the elements of that and find a way to do it that’s safer and applicable to people who don’t have an underlying cancer that would make them undergo a bone marrow transplant? 

IRA FLATOW: Mm-hmm. Dr. Bar, what about other things like vaccines or other work that isn’t getting as much attention? There was a case of a potential cure that got a lot of press coverage earlier this week. One publication actually leaked the news earlier than they were supposed to. What are you excited about? 

KATHARINE BAR: Yeah, that’s a great question. I mean, it is hard not to be excited about the second example of a possible cure. But you’re right and Dr. Cannon is right. This is not directly translatable to a large number of people. 

So when we think about the 37 million people, as you mentioned, who are infected with HIV right now in the world, we want to think about things that are a little more simple and a little bit more broadly applicable. And honestly, the HIV cure research field for those approaches is a little bit earlier on. So we’re looking at strategies to reduce the size of the virus population that is infected and remains in the body despite long periods of HIV medicine. And then we’re looking at novel immunotherapy mechanisms. So a way to train the immune system or enhance the immune system to identify those cells and then clear those cells. 

So you’re right, there are things like vaccines. There are things like antibodies. There’s many strategies that have been used in other types of cancer approaches that we’re looking to apply to the situation of HIV. But I will say that many of these stages are in the very beginning of development. And though there are positive and really exciting developments, we’re not at the stage of being able to even do large stage clinical trials or implement them broadly to all the people who could benefit ultimately. 

IRA FLATOW: Dr. Cannon, what about gene therapy? We hear so much about that. Is that a useful and applicable line of work here? 

PAULA CANNON: Oh, absolutely, yes. And indeed, as we are trying to figure out how to sort of recreate what’s happened with these transplant patients, gene therapy is, you know, really playing a starring role. 

We have two challenges. First of all, we have to figure out a way to sort of debulk the reservoir of HIV that exists in patients. And that’s kind of one of the things that happens when somebody gets chemotherapy for their cancer. We don’t want to have to do that. We don’t have to give people chemotherapy. So instead, we’re trying to sort of figure out kinder, gentler, more sort of targeted ways that could specifically remove HIV-infected cells. 

But then that’s not going to be enough because we’ll never be able to get rid of all of the HIV. And so what we want to do then is use gene therapy to take some of the patient’s own cells and make them resistant to HIV to sort of mimic what happened with these donors of the bone marrow transplants. 

And in 2019, and it sounds crazy to me that I can even say this, but doing gene therapy to recreate the genetic quirk that these HIV-resistant donors had is almost becoming routine. You know, we have amazing tools, like CRISPR, for example, that allow us to go in and target the specific gene that can make people’s cells resistant to HIV, a gene called CCR5. 

And so that part of the treatment, that part that gene therapy can do, I kind of feel like, you know, we can do that already. But what we don’t know is if that’s going to be enough. And instead, what do we combine that with to kind of, if you like, debulk people’s HIV reservoir. 

IRA FLATOW: If you can you think do gene therapy, that kind of work already, are there trials with gene therapy? 

PAULA CANNON: Yes. Indeed. And there’s actually trials going on already where people’s own bone marrow stem cells have been taken out, and with reagents that are a bit like CRISPR called zinc-finger nucleases, they act like genetic scissors and they are mutating this gene, the CCR5 gene in the patient’s own stem cells, which are then kind of returned to them. So there are ongoing trials in Los Angeles looking at whether or not that can help patients, if not completely cure them, at least give them some benefit and some way of controlling the virus. 

IRA FLATOW: Katharine, let me ask you, what makes HIV such a hard disease to research? Is it just that the virus is a complicated problem? 

KATHARINE BAR: Yeah, the virus is a very tricky adversary. You know, it’s a small virus, but it’s very flexible and it changes quickly to sort of fight off whatever strategy we use. So it can quickly develop resistance to HIV medicines. And that’s why we have to use multiple medicines at the same time in order to even suppress it effectively. Not eradicate the reservoir for cure, but just to maintain suppression. 

But the other thing that makes it really tricky is that it’s a type of virus called a retrovirus, which means it takes a copy of its DNA or its genetic material and puts it into the host’s cell. And so shortly after infection, just a very short period of time, the virus embeds itself permanently in an HIV-positive person’s body. And so that that window to prevent the seeding of HIV is very, very narrow. And so basically, every person who becomes infected with HIV has these permanent copies within their own cells. And that’s this major barrier for HIV cure, that all of the research is sort of trying to reduce and hopefully completely clear. 

IRA FLATOW: More and more we’re seeing the overlap between cancer research and HIV. As you point out, both of these men involved in this cure had cancer, and treating the cancer also got rid of the virus. Does it mean there are still other things from cancer treatments that we could apply to HIV? 

KATHARINE BAR: Yeah, I think that’s actually a very exciting area of research. We are borrowing a lot of immunotherapeutic strategies, as well as a lot of the knowledge that cancer researchers have gained from exciting, new, and really groundbreaking treatments in cancer. 

But one of the problems is, you know, when you think about someone who has a life threatening cancer that maybe cause their death in three to six months, you’re really willing to take a lot of risks in order to try to extend that person’s life. So side effects or toxicities for very exciting therapies are tolerated in that situation. 

But when we talk about a HIV-positive individual who’s doing well on HIV medicine and really living a very functional life, we’re not willing to entertain serious toxicities. And so that margin or that window of what we’re able to tolerate in order to see the effects of these exciting immunotherapy strategies is much smaller. And so that’s one of the limitations of applying many of these exciting immunotherapy strategies that are currently being so successfully employed in cancer. 

IRA FLATOW: Are you limited by the number of candidates who have both cancer and HIV, finding them? If you want to test out something? Paula, what do you think? 

PAULA CANNON: Oh yeah, no. Absolutely. I mean, you know, really, if you have a blood cancer and you fail the initial treatment so that you then become a candidate for a bone marrow transplant, it’s almost like, you know, the planets have to be aligned and you know, you have to have HIV, have a blood cancer, need a bone marrow transplantation, and then find a donor who is not just what we call a tissue match, somebody who can serve as your bone marrow donor, but who also has this rare genetic mutation, the CCR5 mutation that only about 1% of the population do. So you know, it’s always going to be a very, very unusual circumstance. 

But one of the things that I think is quite exciting is increasingly, you know, cancer doctors know about this, there’s a large consortium in Europe called IciStem, which is– actually it’s funded by the American Foundation for AIDS Research, which is the charity that Elizabeth Taylor set up. And they are putting together a database of potential bone marrow donors who are carrying the CCR5 mutation. You know, they’ve got more than 20,000 people on their books, if you like, ready to go. 

So although it’s always going to be a very unusual and only be possible in a small group of patients, I think what’s exciting is that that’s going to be made available to people who qualify for that and who want to undergo that treatment. 

IRA FLATOW: Well, thank you both for taking time to be with us today. Dr. Paula Cannon, Professor of Molecular Microbiology and Immunology at the Keck School of Medicine at the University of Southern California, LA. Dr. Katharine Bar, Assistant Professor of Medicine in the Infectious Disease Division at the University of Pennsylvania in Philadelphia. Thanks again for taking time to be with us today.

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Ira Flatow is the host and executive producer of Science Friday. His green thumb has revived many an office plant at death’s door.

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