Researchers are exploring a new approach to fighting HIV infection by genetically modifying a person’s own immune cells to be resistant to the virus. The work, the researchers say, could eventually help people control the virus without drugs. Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases, discusses a report about early safety studies on the technique published this week in The New England Journal of Medicine.
Anthony Fauci is director of the National Institute of Allergy and Infectious Diseases at the The National Institutes of Health in Bethesda, Maryland.
IRA FLATOW: This is Science Friday. I’m Ira Flatow. This week, hopeful news in the fight against HIV and AIDS. A study of monkeys found that injections of antiviral drugs could keep working for weeks at a time, a finding that could lead to more convenient treatments. And in another report, a doctor described how large doses of anti-HIV drugs given just after birth may have been able to clear the HIV virus from the blood of a newborn child. And in a third study that sounds something out of science fiction, researchers reported this week in the New England Journal of Medicine that they had removed white blood cells from people, genetically modified those cells to be resistant to HIV, and returned those cells back to the donor.
Are we at a turning point in HIV/AIDS treatment? Joining me now to talk about it is Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases. It’s part of NIH in Bethesda. Welcome back. Always good to have you, Dr. Fauci.
ANTHONY FAUCI: Thank you, Ira. Good to be with you.
IRA FLATOW: Tell me the– let’s work backwards. This third result this week involving a very young baby– tell us about what happened there.
ANTHONY FAUCI: Well, listeners might recall there was a big to-do about a year and a half ago that was called the Mississippi baby, which was a baby that was born of a mother who was infected but had not had antenatal care and so was not given anti-HIV drugs. The assumption was made by the physicians taking care of the baby that the baby was indeed infected, and treated the baby aggressively with the typical three-drug treatment regimen. As it turned out, the baby was on therapy for several months, was lost to follow-up, the mother discontinued drug. And when the physicians finally reconnected with the baby, the baby was off drug, but no detection at all of virus in the baby. And after several months, the assumption, which was reasonable, was made that the baby was cured.
A recent report, similarly, from a California baby who was born of an infected mother who was not treated, and that baby was treated within four hours of being born. And nine months later, even though the baby’s still on drug, there’s no indication that the baby’s infected, because they can’t find virus examining the cells in the body.
The reason these cases are important, because it’s going to be a re-evaluation of how you approach babies born of infected mothers, particularly when the mother has not had prior therapy, because previously there was a little bit of a conservative approach, namely trying to balance the toxicity of a drug, and whereby you might treat a baby who was really not infected, because you can’t tell immediately if the baby is infected. You have to wait a little while. We’re getting better at shortening that period, but sometimes it takes a couple of weeks.
So the balance of risk-benefit was, treat the baby with a less aggressive, more prevention approach, and wait a few weeks to avoid toxicity, and then when you finally show the baby’s infected, then go back on the really aggressive dose, or start the aggressive dose right away. And what we know now is, since you can possibly cure a baby if you treat them aggressively right from the very beginning, literally within hours, then that tips the risk-benefit ratio much more towards being aggressive right from the get-go, particularly when you’re dealing with a baby who was born in a very high-risk situation, namely a mother who’s not had any treatment.
IRA FLATOW: And that’s a lot of babies, isn’t it?
ANTHONY FAUCI: Well, sure. Worldwide, there are hundreds of thousands of babies who are born each year with HIV infection, particularly in the developing world, and particularly in those situations in which the mother may not have gotten any antenatal care. So when the mother walks into an emergency room or a clinic, let’s say in one of the developing countries in southern Africa, right now, there’ll be the consideration that maybe one should be very aggressive right from the beginning.
And in fact, there’s a clinical trial, Ira, that will be started within a period of a few months, probably in May, including in southern African countries, where mothers who have not been given treatment during pregnancy and come into a clinic, when the baby is born, within 48 hours the baby will be treated with the three drugs, assuming that the baby is infected. And if the baby is, then the drugs will be continued. If not, they’ll be lessened and then discontinued.
So we have two cases where it looks really promising. But before you can make any general policy decisions, you really need a larger number of babies followed over a longer period of time. And that’s what that clinical trial is directed at.
IRA FLATOW: Let’s move on to this gene editing paper published this week. Tell us about what they did there.
ANTHONY FAUCI: Well, what the investigators did is that they took cells out of the blood of an infected person who had been on therapy and doing really quite well on therapy, and they modified the cells in the test tube, called gene editing. What they did is that they performed an editing of the gene whereby the cells no longer expressed that critical receptor that’s necessary for the virus to infect the cells. So they made the cells refractory to infection.
They grew them up to 10 billion cells, and then, just like a blood transfusion, reinfused them into 12 people who were subjects in the study. And the real question they were asking is, first of all, is it safe to do? And it is. There were no real problems.
Second is, can they actually grow these cells up that are cells that now won’t get infected with HIV? And when you reinfuse them, will they hang around the body or just disappear? And they found that in fact, they do hang around. And they were pretty successful in getting a substantial proportion of those cells to be modified.
The real bottom line of it all is going to be, will those cells ultimately replace the vulnerable cells so that these people are left with cells that now are refractory to being infected with HIV? And it was a good step in the right direction. Obviously, it wasn’t completely successful, because the virus bounced back. But interestingly, the cells that were modified seem to be less susceptible to getting destroyed by HIV than the person’s normal cells. So that’s a very important step in the direction of trying to see if this gene editing technique will actually turn out to be feasible and applicable to a larger number of people. We don’t know that yet, but that’s where the trials are going.
IRA FLATOW: All right, let’s talk about the third news item this week, a study in which monkeys were given a sort of long-acting anti-HIV drug cocktail. What happened there?
ANTHONY FAUCI: Well, that’s an important study, because we know from several human studies that when you give an uninfected person a daily pill called pre-exposure prophylaxis, and that person is practicing high-risk behavior, if you give that person and they take a pill every day, that you can prevent them from getting infected in their high-risk situation. We know it works. The only trouble is, people don’t like taking a pill every day. And when we go back and reexamine the details of the study, you find out that if people really did take their pill every day, it was effective at about 90-plus percent to prevent infection. Yet if you look at the whole study, it was really only about 40% effective, which means a lot of people were not taking their medicine every single day.
So the study in the monkeys showed that you could take the derivative of a drug that’s used frequently in treatment of HIV infection and inject it into the monkey, and then expose the monkey vaginally or rectally to the monkey version of HIV, and that long-acting injectable drug really very, very effectively prevented the monkeys from getting infected. So the ultimate goal is, if you can get an injectable drug that would prevent infection and give it three or so, three or four times a year, to people, then you could get away from that problem of adherence to taking a pill every day, because we know it works, for sure, but if we get it in the body just with a few injections a year, that would be a pretty good advance.
IRA FLATOW: About a month ago you published an opinion piece in the New England Journal of Medicine in which you said, quote, “The only guarantee of a sustained end of the AIDS pandemic lies in a combination of non-vaccine prevention methods and the development and deployment of a safe and sufficiently effective HIV vaccine.” So you believe that the vaccine is very essential to have this other tool.
ANTHONY FAUCI: I believe so, Ira. I believe we will make major advances and are making major advances in preventing infection, preventing death, treating people with the tools we have now, which is not including a vaccine. But given what we know about human nature, and given what we know, just what we’ve been talking about, about people really having trouble adhering to regimens that work, and given the fact that we want a sustained end to the AIDS pandemic, I’m convinced that in order to get there and to have that sustained in a way it doesn’t just rebound the way other diseases have, we need that combination of many of the kinds of non-vaccine prevention modalities combined with a reasonably effective vaccine. I really do believe that that’s going to be essential.
IRA FLATOW: Is there a parity in the research going on for the treatment and the vaccine sides?
ANTHONY FAUCI: Yes, it’s pretty well balanced. We have a lot of resources invested in vaccine research, a lot of very good investigators throughout the country and the world working on it. And we have a large number of protocols and research projects involved in the non-vaccine prevention modalities.
IRA FLATOW: So is it just an engineering problem now?
ANTHONY FAUCI: No, with the vaccine, Ira, it’s really still a discovery problem, because HIV is such a perplexing virus, in the sense that even when it infects somebody, the body doesn’t make an adequate immune response. And so unlike other vaccines where you just take a look at what nature does and take a look at the normal immune response to a microbe like polio or measles or whatever, you can then mimic your vaccine to induce that response. The trouble with HIV is that the natural immune response to HIV is not particularly adequate in controlling the infection and certainly not in eradicating the virus.
So we have that very, very difficult task of doing even better than what natural infection does. So we’ve got to go one step further. So it’s still a question of discovering really what the best approach is, as opposed to just an engineering thing where you just have to manufacture the vaccine.
IRA FLATOW: Right. Well, Dr. Fauci, once again, thank you very much for taking the time to be with us today, and good luck to you.
ANTHONY FAUCI: Thank you very much, Ira. It’s always good to be with you.
IRA FLATOW: Thank you, Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases. And that’s part, of course, of NIH in Bethesda, Maryland.