Jackson Free Press

The headlines screamed the news across the globe: "Baby Cured of AIDS!" They weren't entirely accurate; nonetheless, the news thrust pediatrician Dr. Hannah Gay into the harsh glare of the spotlight last March.

Gay's patient, a toddler born to an HIV-infected mother in 2010, tested positive for the infection at birth and for several months while under Gay's care. Then, she and her mother stopped showing up for treatment. When the baby returned to the University of Mississippi Medical Center about 18 months later, clinicians could not find the virus in her blood.

A soft-spoken and fiercely intelligent woman, Gay insists that she didn't cure the child. The treatment she used was within the parameters of what she would use with any patient under the same or similar circumstances.

"I'm getting credit in a lot of the press, for 'discovering' the cure, or 'developing' the cure, and I'm going, 'Wait! I was as surprised as anybody!'" Gay said.

She gives full credit for the child's healing to God, and in retrospect, she can easily see the small miracles all along the path. "I just happened to be standing close by," Gay said. "I obviously was not trying to cure the baby. Cure was the furthest thing from my mind."

To imply that she has a cure for HIV, human immunodeficiency virus, the therapy must be proven in more than one patient, which has yet to be done. It's also unlikely that the specific results could be achieved in adults. None of that stopped the mainstream press, though.

In April, Time magazine named Gay and two colleagues, Katherine Luzuriaga, an immunologist from the University of Massachusetts, and Deborah Persaud, a virologist at Johns Hopkins Children's Center, to its 2013 list of the 100 most influential people in the world for their contributions to the field of HIV research.

Gay has yet to become comfortable in the role of spokeswoman for Mississippi, UMMC, and the army of doctors and researchers working in the HIV/AIDS field. Clearly, she'd rather be working with children than talking to reporters or speaking at conferences, but she gracefully and generously accepts the need to do so.

In August, Gay granted the Jackson Free Press a wide-ranging interview that ran almost two hours. The edited version is below. You can read the entire interview on the JFP website.

If a mother is HIV positive, at what point can the virus be transmitted to the child?

Most transmission from the mother to the child occurs during the labor and delivery process. A smaller group, a minority, probably less than 10 to 15 percent, are infected in utero, during the pregnancy. But those almost all happen near the end of the pregnancy, in the last few weeks.

The reason we know that they're not infected prior to the delivery is that those who are infected at labor and delivery usually have negative tests at birth. This is kind of an artificial line that's been drawn, but we say if the baby has a positive virologic test prior to 48 hours of age, then we call that an in-utero infection.

So if the baby tests negative at birth, where do you go from there?

The national guidelines here in America are that we test at two weeks, and then between one and two months, and then again (at) four to six months. We do a little more; our routine here at UMMC is that we test at two weeks, one month, three months and six months. Those are all by what we call virologic tests. It's a very specific test looking for the HIV nucleic acids.

For an adult, we test antibodies to see if they have the virus. But that doesn't do us any good with babies because the 
baby does have the maternal antibodies, the antibodies cross the placenta. So a baby who is born to an infected mom 
will be antibody positive for up to 18 months. By 18 months, they have lost the maternal antibodies.

Back when I first started working (in this field), we had to wait 18 months before we knew if the child was infected. The kind of test that we do now, the nucleic acid testing, we can tell much earlier. So, like I said, we test at two weeks, one month, three months and six months. If all of those tests are negative, by the nucleic acid test, that baby is not infected.

In the early years of AIDS research, there was this meme that said, "If you sleep with one person, you sleep with every person that one has slept with." In other words, there's an incubation period for the virus to show up. How does that apply to babies?

For an average adult—and there are no average adults—(and) looking at a big group of people ... from the time they're infected to the time they start showing symptoms, (it) may be as long as 10 years. For a baby who's infected at birth, that period is shortened.

Because an adult who gets infected starts developing antibodies to the HIV, the infected immune system actually controls the HIV for what can be a very long period of time. Babies are relatively immuno-suppressed. The immune system normally develops over the first five years. So a baby doesn't mount the immune response to the HIV virus.

Before we had the anti-retroviral treatments that we have now, we used to say, "OK, an adult may start showing symptoms at eight to 10 years out, and then die, more than likely, some time after that. A baby who is infected at birth is likely to show symptoms at 1 to 3 years (of age), and die at 5 to 8." It was rare that we saw prenatally infected infants make it to their teenage years back when there was no therapy.

Now, however, HIV is no longer a fatal illness. It's a chronic, treatable illness. For my patients, I liken it to diabetes. It's a bad disease. It can kill you. But if you take your medicines and do the right things to take care of yourself, you can life a long, healthy life with the disease.

When the news was announced in March that this baby had been functionally cured, some people mistakenly assumed that this is the end of AIDS. What is the landscape of AIDS right now?

In the West, it is a chronic, treatable illness. In resource-poor nations, it may not be as easily treated simply because of not being able to get the treatment to the patient. In many parts of the West, it is no longer on the rise like it was for a long time.

Who is most at risk?

In the South, most of our transmission is through heterosexual contact, and it's much more prevalent in African Americans and Hispanics, women and men both. There are more men who are infected, but women are more likely to be infected through heterosexual contact. We do have some IV drug users who infect that way, but not nearly (as many).

So it's still on the rise in the South.

Do people believe HIV and AIDS are no longer much of a risk?

I'm afraid that's what's happening.

... In 1994, we had, across the nation, about 25 percent of babies born to infected moms were infected at birth. There was a large-scale study that was done that showed that if you treat the mom during pregnancy, and then we were also treating the mom with IV medicine during labor, and then treating the baby for six weeks afterwards, that you could reduce the risk of transmission down from that 25 percent average down to 8 percent average.

That's huge.

Huge, yes. Really huge. So in 1994, here in Mississippi, we started a program to implement that information. When I actually started this job in 1994, a big part of my job was to implement that in Mississippi where we started treating moms. At that point, we only had one drug. There were two on the market, but only one that we could use during pregnancy.

So at this point, are HIV-infected babies rare?

In the West, they're very rare because we do an awful lot to search out, find the moms who are infected during pregnancy (and) be sure we treat the moms adequately.

As a virus, HIV is constantly mutating to resist whatever you're trying to bombard it with, right?

Exactly. And that's why we use three and four-drug combinations in treatment, so that if you have a virus that's resistant to drug A, you've still got drugs B and C trying to eliminate that virus before it takes over the whole population.

Back early in the epidemic, we created a lot of the resistance due to the fact that we only had one or two drugs. The virus was becoming resistant to those one or two drugs we had. We treated patients with sequential monotherapy—as a new drug would come along, because that's all we had. Now we wish it had been different, because we had some patients who have multi-drug resistance.

Nonetheless, in the last few years, in the last five years, there have been two, actually three new classes of drugs that have been discovered. When we can talk the patient into being truly compliant—I'm not going to say that in every single case we can treat them adequately—but I haven't run into any kids that I've been unable to treat. Not since we've had the modern drugs.

There's a lot of talk lately about drug resistance.

Superbugs.

Talk a little bit about that in the spectrum of infectious diseases. And also rumors—such as vaccines are responsible for autism.

Right. There have been huge studies, meta-analysis of many huge studies put together that show no basis in fact on that.

I kind of go back to what my mother said when she started hearing about mothers who didn't want to have their children get vaccines. She said, "They just don't remember when, every summer in the hot South, when polio started going through." And (my mother) does.

Even when I was a baby, there was still polio every summer. She said, "We were all so relieved, climbing over people to get vaccine for our child."

I was still in preschool, I think, when we all had to go to elementary schools on three Sundays to get our sugar cube to get a polio vaccine.

I remember that, too: lining up for that sugar cube.

I feel like that people who have this philosophy against having the children vaccinated are thinking, "OK, at least in my imagination, there's a possibility that my child will have autism or something if they get vaccinations." They're not thinking about the fact that "If my child has measles, he may get encephalitis and die. If my child gets mumps, he may be deaf for the rest of his life. If my child gets chickenpox, he could have shingles as a result."

They don't think of these diseases. And now, we've got vaccinations for hepatitis B, which kills or becomes chronic illness. We've got vaccinations for H flu (haemophilus influenzae, an opportunistic bacteria can cause a range of illnesses from pneumonia to meningitis to infectious arthritis). When I was a resident, even, we would have two or three cases a month with babies coming in with H flu meningitis. We never see that any more.

With everything, from vaccines on, you have to do a risk-benefit analysis. I think that ... people are not trained at thinking in that way.

So you're saying there's no connection between vaccines and autism, right?

Right.

I heard you mention in a talk you gave that it wasn't you who affected the cure for the AIDS baby. It was God, and you were there.

Yeah. I just happened to be standing close by.

I obviously was not trying to cure the baby. Cure was the furthest thing from my mind. I was simply doing post-exposure prophylaxis.

We talked about how if we treat the mom, then the baby's at very low risk. ... This mom had not been treated, and we didn't know what her viral load was. In cases where—even if we have treated the mom, but not adequately—if she's got a high viral load, that's a high-risk baby. If other factors intervene, and I've got a high-risk baby for any reason, then my first effort is to prevent that baby from being infected by starting early post-exposure prophylaxis.

We do the same thing with, for instance, needle-stick injuries. If one of my nurses is drawing blood and gets stuck with a contaminated needle, she immediately starts HIV drugs as post-exposure prophylaxis. With sexual assault cases that I see in the ER, if there's been a significant exposure and possibly HIV involved, then I start that kid on post-exposure prophylaxis.

We use three drugs. ... We use the same drugs that we use on an infected patient. That post-exposure prophylaxis alone has been shown to reduce the risk of conversion, if it's started early enough. For occupational exposure, or non-occupational exposure like rape, we start the post-exposure prophylaxis as quickly as possible and within 72 hours. After 72 hours it probably has no effect whatsoever.

When this baby was born, knowing that the baby was at higher risk, I started three drugs.

Our national guidelines at the time, this was back in 2010, didn't actually give a recommendation for what to do or what to start in babies who were at high risk. The guidelines said something to the effect of, "In cases were the mom has not been treated, some experts would use more than one drug as post-exposure prophylaxis." It recommended that you consult the pediatric-HIV expert in your area.

So I looked around for one (swivels her head and laughs).

And there you were!

My choice was to start three drugs, which is the same thing that I would do for a needle-stick injury or an assault. I used the three drugs that I would most commonly start in a newborn that I knew to be infected.

Since 2010, our guidelines now address the issue. There was a study that was actually going on at that time, but now we have the results of the study. On the study, there were three arms (of research): One (study) arm got AZT only; one arm they got two drugs; one arm they got three drugs. What it showed that (the last two) arms were superior to the AZT-only arm. These (two) were equally effective at preventing infection, but the three-drug arm carried a little bit higher risk of side effects like anemia or a lower white blood count.

So, in the guidelines, they say, "(Monotherapy) doesn't work as well to prevent infection, so we're not going to use that. (The second and third) work equally, but the (third) causes a little more side effects, a little more risk with the therapy. So, we're going to recommend in our guidelines that you use two drugs for post-exposure prophylaxis if the mom has not been treated."

That's what's in guidelines now.

There's some art to medicine, and there's some use of basic logic. My basic logic that I was using at the time—and I didn't have to go through all this in my mind for that particular baby because I'd already done it, and it's what I was doing for all high-risk babies: using those three drugs. My philosophy was that if we can easily monitor for the (side effects), if those occur—and actually I've never seen it occur to a degree that I've ever had to do something about it—if they did occur ... then we could stop the medicines and the counts would come right back up. So it's totally reversible—easily monitored for and reversible.

HIV, on the other hand, is not reversible. If I use only two drugs, and then that baby turns out to be an infected child who's going to have to have therapy for the rest of their life, the risk of using only two drugs in that six weeks is that the virus would develop resistance to, particularly, one of those drugs that has a very low barrier to resistance. And then, I don't want to have to treat the child for the rest of his childhood with him already resistant to one of my classes of drugs. My reasoning leads me to say it's really safer to go ahead and use the three drugs.

One of the things I see in many religious communities is a resistance to science. You're a scientist, and you're also a woman with great faith. How do you marry those two together?

I was a person of faith before I became a scientist. For me, it's been very, very easy because as I studied science, it reinforced my faith in God. It didn't tear it down.

I remember very distinctly as a freshman in medical school, studying in embryology, and looking at all of what it takes to go from an egg and a sperm to a baby, and thinking, "Only God can do that." It's not something that can be programmed somewhere.

To me, everything that I've studied in science has reinforced my faith, that God is active and in control.

With this particular baby, there's no way to—actually, without putting you through medical school—to point out all of the actual miracles that occurred to make this case come to light. One of them, a very simplistic one: This mom went into labor, went into this outside hospital, they drew (blood to test for HIV), which is standard thing. If you don't have a negative HIV test on the chart from the first trimester and last trimester, then you do one when they come in labor.

They drew the test, and ... they got back, at this rural hospital, a positive screening test. That automatically kicks it over into sending it off for a confirmation test: a western blot. They sent it to a reference lab to have the western blot run.

Now, I have never, here at UMMC, gotten a western blot back in less than three days. Usually, it takes us five to seven days to get the results on a western blot test. When this baby got over here, we knew that mom had a positive screening test. We were very suspicious that (the baby) was indeed infected, but we did not have confirmation that she was infected. When the baby got here, the first thing that I did was to start AZT alone. I did not want to start three drugs on a baby without knowing that he was even exposed—you get back to the risk-benefit thing.

About 30 minutes after the baby got here, the outside hospital called me and said, "We just got back the western blot from the reference lab, and it's positive." It was less than 24-hours from the time it was drawn at the outside hospital.

I didn't believe them. I said, "You fax me a copy of that. I've never gotten a western blot back that fast." They faxed it over. It showed that she was, indeed, infected. I imagined very high viral loads, and started the other two drugs. Actually, the baby got started on AZT about an hour ahead of the other two drugs.

But an hour, not days, not weeks.

Right.

I'm convinced that it was God's hand to have that western blot come back that early. There were a number of things like that that happened along the way.

... All of these little things, these little definitions, of course didn't become significant until a year and a half later, or nearly two years later, when we're trying to figure out what happened. But to present this to the scientific community, you've got to be able to say, "I had two separate samples."

We had three other samples because, having gotten back (the first two) positive, I kept her on the medicine. We kept drawing viral loads to watch her viral loads coming down on therapy.

All of that became important, not at the time, but later on when we're trying to make the case that yes, this child was definitely infected. And now she's definitely not.

So you had steps that you can see in retrospect. Has any of that been reproducible?

We have not found another baby that we know has fit in this category.

What we have known for a long time is that babies who are infected, who are treated early ... at less than three months, ultimately do much better than children who are started on treatment later.

... Babies who are being treated at three months or less very often don't even make antibody to HIV because the amount of virus that they have in their blood, in their viral reservoirs, is so minute that their system doesn't even recognize it as there.

... Our advantage in pediatrics, of course, is that we know the time of exposure. Most adults don't.

... My baby had the measurable virus until she was 26 days of age and the medicines controlled it. Then, when she came off of medicines, her virus didn't come out of any reservoirs. We can't find any virus in the reservoirs. So, it has never reappeared, even to the extent to make her make antibody.

She, at this point, is negative by RNA test, which shows free virus in the blood. She's negative by our DNA test, which shows virus in the reservoirs, in infected cells, and she's negative by antibodies.

So, it's like she never had it at all?

Right. By all of our standard tests, she looks like a child who never had HIV. And yet we know that through the first month of life, she had it. She had five separate virologic tests.

Other than, "It's a miracle," is there any way to explain this?

Our hypothesis is that what happened is, by starting the medicines at 30-hours of age, we were starting to prevent the viral replication. The amount of virus in her blood was dropping like a rock, just like it normally does with treatment. We think that by treating that early, we prevented the virus from every seeding the viral reservoirs.

What we know happens with adults is that when you're first exposed, the 
virus gets into the blood, it starts attacking and entering the CD4 positive cells (cells that initiate the body's response to infection), the cells that have CD4 (glycoprotein) on their surface. Most of those cells are activated T-cells. Inside those active T-cells, the virus starts replicating very rapidly.

At the same time, there are some, what we call "resting" T-cells. They are also CD4-positive, and they also can get infected. But inside the resting cells the virus doesn't replicate. It can live there for as long as the cell lives, but it doesn't replicate inside a resting cell. The resting T-cells are what we call "T-memory" cells.

If you're 57, you probably had chickenpox as a child. When you had chickenpox, you formed T-memory cells to chickenpox. When you're exposed to chickenpox again, those T-memory cells become active. They fight off the virus before you can get chickenpox. That's why you don't get chickenpox twice.

Those T-memory cells can be very long-lived. They can live for many, many years. Any virus that gets into that chickenpox T-memory cell can stay there and stay alive as long as the cell lives.

That's the biggest portion of what we call viral reservoirs. It's those long-lived T-memory cells that got infected back at the same time as the exposure, but they're sitting there in latency. The patient may be taking their medicine and clearing the viral replication going on in all the activated cells, but once he stops taking the medicine, there's this reservoir waiting to receive the blood.

Waiting like little time bombs.

Our advantage, with the baby—the baby doesn't have T-memory cells. They start developing T-memory cells as they're being presented with antigen. So somebody who's never seen chickenpox doesn't have any chickenpox T-memory cells. A newborn doesn't have many T-memory cells at all.

Therefore, what we think we may have done—our hypothesis in this case—is that by clearing the replicating virus out of her active cells early on, we prevented it from ever getting to those newly forming T-memory cells—easier to do in a baby than in an adult because the adult already has T-memory cells on the day of exposure.

That's our hypothesis. To prove the hypothesis, we're going to have to replicate this. There's going to be a study, hopefully starting in the fall, or the first of the year, where they're going to take a number of high-risk babies—moms have not been treated (prenatally) so they're at high risk—and they're going to start the same three drugs I used as post-exposure prophylaxis in the first 48 hours of life.

At age 6 weeks, they will test the baby. If the baby tests positive, that it is an infected child, they will actually add a fourth drug, keep the baby on four drugs for three years. At the end of three years, they will start testing using these ultra-sensitive tests that are only available in the research labs to look and see if they can find any replication-competent virus in the reservoirs. If they can't, then they'll stop the drugs to see what happens.

All of that said, if that study replicates it, it's going to kind of at least semi-prove our hypothesis. It will at least show that very early treatment works.

And works definitively, correct? So the expectation is that this child is never going to show HIV virus again.

That's our expectation. I'm still paranoid, so I see her every two or three months and draw another viral load and just check to see. We have repeated cultures in the end of May, we repeated cultures yet again, and we have still to see any replication-competent virus.