"Surviving AIDS"

PBS Airdate: February 2, 1999
Go to the companion Web site

NARRATOR: Princeton University. The annual celebration of class reunions. As far back as the class of 1923, men and women who've survived decades gather to reminisce, see old friends, and catch up.

But in the class of '78, there's one man no one expected to be here. The year he graduated, Bob Massie was infected with H.I.V., the AIDS virus. A hemophiliac, he got H.I.V. from contaminated blood clotting factor. At the time, it was a death sentence.

BOB MASSIE: People would say, H.I.V. is a fatal illness, although you can go as long as...blank years before you fall ill. And the blank was always whatever number it had been for me. So when people would say, well, you can go as long as five years, and I was five years out, and then, you can go as long as seven years, and I was seven years out—Some people can go as long as ten years, and I was ten years out. So, there's always this sense that I was right sort of at the limit.

NARRATOR: But, against all odds, Massie, an Episcopalian minster, has stayed completely healthy. His survival, both a miracle and a mystery, is inspiring a whole new approach to fighting AIDS.

DAVID BALTIMORE, MD: There are people walking around, and Bob Massie's an example, who have been infected for almost twenty years, and they're doing incredibly well. If we can understand what's going on in them, we may be able to take that knowledge and use it to our benefit in people who presently aren't controlling the virus.

NARRATOR: In labs and hospitals across the country there are bold new experiments going on, as researchers step into the unknown, and patients put their lives on the line.

These adopted twins are infected with H.I.V. At two months old, they were the youngest patients, ever, to be given powerful anti-AIDS drugs. No one knows what their future will hold.

__: If we run out of drug therapy, then they might say, someday: Oh, we shouldn't have used all our drugs in the beginning. And if you get to that point, then it's too late.

NARRATOR: Other patients are volunteering to stop those same life-saving drugs, to see if survival is possible without them.

__: These people are heroes. Whatever information we can glean, we've found a group of individuals who are willing to put the greater cause, potentially, over their own well-being.

NARRATOR: The courage of a few individuals may open the door for millions of AIDS victims, and this era of new hope has come not a moment too soon. With the epidemic well into its second decade, the National AIDS Memorial Quilt has become an all-too-familiar symbol of the 500,000 Americans, and 11 million people worldwide, who have succumbed to AIDS.

STEVE CROHN: What's hard is living with the continuous grief. You kept losing people every year—six people, seven people. Last week, a friend of mine's obit. was in the paper. It's not easy, when you're losing friends and you're that young, and it goes on for such a long period of time. And the only thing you could compare it to would be to be in a war.

NARRATOR: The war began when the AIDS virus was discovered, in 1984. It is one of the most formidable enemies science has ever faced.

ANTHONY S. FAUCI, MD: There are still many, many mysteries about how the body reacts to, protects itself against, or suppresses H.I.V. that are unanswered, and one of the reasons why they're unanswered is that we're dealing with such a unique virus.

NARRATOR: The AIDS virus is unique in part because it attacks the immune system, the very cells in the body designed to fight off invaders. Carried through the bloodstream, the virus injects its genes into the immune cells of its victim. Each infected cell becomes a breeding ground for the deadly H.I.V. virus. Slowly, but relentlessly, the immune system is destroyed.

Many of these scientists have dedicated the past 15 years to AIDS research, especially the struggle to come up with a protective vaccine.

DAVID BALTIMORE, MD: From the very first moment that the virus was discovered, a vaccine was on people's minds, and there has been a significant effort to make a vaccine, from the very first day. And I think people thought it would be simple, because we'd made vaccines for so many different viruses.

NARRATOR: But H.I.V. belongs to a particularly devious family called retro viruses. There has never been a successful vaccine against a retro virus. And many scientists are beginning to believe that a vaccine against AIDS may be impossible to make and too dangerous to test.

DAVID BALTIMORE, MD: If you take it, and then a year goes by and everybody's fine, then you say, OK, that's good, now let's give it to 500 people; and then a year goes by and everything's fine. You say, Well, then, now let's give it to thousands of people, and then you find out that it takes twelve years for all hell to break loose, and then what have you done?

It's been an enormous struggle, because the obvious things didn't work, and people got very frustrated by that. And then the next question was: Where do you turn? What's not obvious? What can we do?

NARRATOR: It's a question that takes on special urgency at places like this—Massachusetts General Hospital, in Boston, a leading center for AIDS treatment and research.

This lab was the first to show that combinations of anti-viral drugs, the AIDS cocktails, could prolong life for many patients—the first real ray of hope in the epidemic.

Now, scientists here are looking for the next breakthrough.

BRUCE WALKER, MD: I think if you go back five to ten years, the entire emphasis was on trying to develop drugs that could be given to patients to make them better. What's changed dramatically is that we've slowly gotten a sense that there may be another factor that may be able to contribute to people doing better, and that's the immune system, that's the body's natural defenses against viruses.

NARRATOR: It was 1994 when Bruce Walker met the patient who would help turn his thinking toward the immune system: Bob Massie.

BOB MASSIE: I didn't know what to expect. And he came in, and he was such a friendly and interested fellow, and when we started to describe what my situation was and he looked at some of the numbers that had come back or that I'd brought with me, he was so excited and so enthusiastic that it was actually quite charming.

BOB WALKER, MD: He came, said, I've been infected for 16 years, but I feel great, I've never taken any drugs. We thought that was already interesting. But when we got his viral load back, we became incredibly interested.

NARRATOR: Lab tests showed that Massie did have antibodies against H.I.V. in his blood, proof he was infected. But, to Walker's surprise, the virus was not multiplying wildly, the way it normally did.

ANGELA ALIENDO: What we have here is a viral load assay, which measures the amount of H.I.V. RNA in the patients blood. This is a patient that has acute H.I.V. infection, and you can see, the yellow color goes all the down to the final dilution here. There's a very high amount of virus in this patient's blood, greater than a million copies.

And this last vial here is Bob Massie, and he has no yellow color at all, and has undetectable viral load.

NARRATOR: Without any drugs to control the virus, Massie's natural immune defenses seem to be holding H.I.V. in check—an unheard of idea.

Walker and his colleague, Dr. Eric Rosenberg, embarked on a quest to unravel this mystery. They began at the most basic level of immune response: two sets of white blood cells called CD-4 helper T cells and CD-8 killer T cells.

CD-4 helper cells are the first line of defense against any invading virus. They send chemical signals to the rest of the immune system to begin an attack. When summoned, CD-8 killer cells marshall their force and eradicate the virus. But H.I.V. overwhelms the helper cells before they can sound the alarm. That leaves the killer cells without direction, helpless against H.I.V.

BOB MASSIE: So, where is this sample going?

ERIC ROSENBERG, MD: This sample is going back to the Mass. General, and, then, there's several different investigators who have experiments that they want to do within our lab, so—

NARRATOR: When Eric Rosenberg and Bruce Walker started analyzing Bob Massie's blood, they discovered something amazing: his killer cells were doing exactly what they were supposed to do.

BRUCE WALKER, MD: We had developed a theory already that killer cells were an important component of an effective immune response, and so we looked in Bob to see if had killer cells present, and what we found was that not only did he have killer cells present, but he had enormous numbers of killer cells.

NARRATOR: Once Walker knew that Massie's killer cells were working, the next question was, How is that possible, if his helper cells had been destroyed by H.I.V.? The answer was a complete surprise: Somehow, Bob Massie's helper cells had escaped the virus and were leading an incredibly strong immune response.

BRUCE WALKER, MD: Not only did he have a helper cell response to H.I.V. but he had a phenomenally large helper cell response.

__: We're all amazed—we though that people who were H.I.V.-infected just didn't, weren't able to, mount this type of immune response, and here was somebody who clearly did, and did it in a way that was never seen before.

NARRATOR: Massie was breaking all the rules. His natural immune defenses were keeping H.I.V. under control. He's called a long-term non-progressor, and he's not the only one. About five percent of people infected with H.I.V. are surviving, for years, without illness. Understanding these patients could be critical to saving millions of people who would otherwise die of AIDS.

Up until now, the best available therapy for controlling H.I.V., in this country, has been combinations of powerful drugs that stop the virus from multiplying in the body.

__: So, have you noticed any difference in any of this since I last saw you?

__: No, I haven't.

NARRATOR: The AIDS cocktails have kept many patients alive much longer than would have been imaginable at the beginning of the epidemic; but as they are more and more widely used, life-threatening side effects that no one expected are developing, like diabetes, high blood pressure, and heart disease.

__: The side effects that we fear the most, obviously, are those kinds of side effects that affect internal organs and can make people quite ill, or cause them to be admitted to the hospital. And it's possible that long-term side effects of these drugs will turn out to be worse than we anticipated, and I think patients are extremely aware of that risk.

NARRATOR: The cocktail drugs are also enormously expensive: an average of $15,000 a year for patients, and, almost half the patients who try cocktail therapy do not get better. They develop resistance to the drugs, or the drugs simply don't work.

BRUCE WALKER, MD: For those of us that take care of patients, we're coming to the unhappy realization that, for many patients, these drugs are failing, and we're left without a whole lot of other options.

NARRATOR: In the face of this hard reality, the stakes are high, as the Mass. General team struggles to unlock the secrets of Bob Massie's remarkable survive.

BOB MASSIE: I began to see the significance of some of these things when Eric would arrive and he would jokingly refer to me as "the gold standard." He'd say, "I need to draw a little more from the gold standard." I said, at one point, my code name, you know, in the research was 161-J. I learned this, and I thought, Well, you know, the irony is that all the other things I'm doing in my life, books and other activities, I may end up being more well-known as 161-J than anything else.

NARRATOR: It is only now, twenty years into the epidemic, that scientists are grasping the significance of that small group of people who break the rules of AIDS infection. One of them is Steve Crohn, a witness to the earliest days of the epidemic, in a very personal way.

STEVE CROHN: In January, 1978, Jerry Green, my partner, became sick with flu-like symptoms, and that continued, for a while. Jerry's progression of his disease went on for fifteen months, in which time he suffered a number of debilitating, wasting—He went blind in one eye, he had cylimegala (?) virus. When he actually passed, on March 4, 1982, there was no such disease as what we call AIDS.

NARRATOR: But, in fact, Crohn's partners was one of the first deaths from AIDS in the U.S. When the H.I.V. virus was discovered, in 1984, Crohn worried that he'd been infected.

STEVE CROHN: There is always this underlying suspicion that, sooner or later, it might find its way into my system, and not because I had lived a very promiscuous life style but just because there was something out there that was invisible, that was transmissible by blood products, or human or vaginal uses, whatever, and that were you exposed. And there are a lot of people that don't know how to take care of themselves.

NARRATOR: But despite repeated exposures to H.I.V., Steve Crohn remained uninfected.

STEVE CROHN: I don't know why I was surviving. I remember talking about with somebody, at a family party, and they said, Well, why aren't they studying you? Like, when you look at families, all the children have some malfunction, or bone—or some genetic disease, or whatever, they study the child that is not. And most of the studies were not studying H.I.V.-negative people, at all.

NARRATOR: Crohn volunteered for a study at the Aaron Diamond AIDS Research Center, in New York. Dr. David Ho, a pioneer in anti-AIDS cocktail therapy, is now looking for new ways to attack H.I.V. by studying people who have resisted infection.

DAVID HO, MD: I think we have learned, in science, that by studying outliers, the extreme result, here and there, you could really learn a great deal about what is happening in the normal situation.

NARRATOR: Ho took cells from Steve Crohn's blood and flooded them with H.I.V., in test tubes.

DAVID HO, MD: He and one other person turned out to have cells that were resistant to H.I.V. infection, while the cells of others were readily susceptible to H.I.V. infection in the test tube. And initially, we thought that was a mistake in experimentation, but upon repeated testing, it gave us the consistent result—that their cells were resistant to the prevalent strains of H.I.V.-1.

NARRATOR: If Ho could figure out why Steve Crohn was immune to H.I.V., the potential was obvious: a way to protect millions of people against AIDS.

H.I.V. affects the immune system by binding to protein receptors on the surface of CD-4 helper cells. One type of receptor was identified, but it was not enough. Binding to this receptor alone would not allow H.I.V. to penetrate the cell. Perhaps a second receptor was needed. But it would take more than ten years for scientists to find it.

When they finally did, in an explosion of discovery, five different labs, including David Ho's group in New York, announced they had isolated the second receptor for H.I.V., called CCR-5.

DAVID HO, MD: For H.I.V. to penetrate into a cell it needs to have a dual docking mechanism at the surface of the cell. So, H.I.V. will use its own protein, the outer protein, to bind to two different cellular molecules, and H.I.V. will bind to CD-4 first; it then changes its structure, after binding to CD-4, and therefore the new structure would then bind to CCR-5, and that would cause the two membranes to fuse, and H.I.V. then enters the cell.

NARRATOR: Since the CCR-5 receptor is a proteins, and proteins are produced by genes, the next question was whether there might be a genetic reason why some people did not get infected by H.I.V.

The role of genes in the AIDS epidemic is the focus of the Laboratory of Genomic Diversity at The National Cancer Institute.

STEPHEN J. O'BRIEN: Human genetics is traditionally thought to involve heredity diseases that we inherit from our parents, but there's something of the order of two or three million genetic differences between every individual of the human race, and those differences affect a lot more than heredity diseases; they also affect our appearance, our behavior, our immune response, how quickly our hair grows gray, whether it falls out, and how fat we get. And one of the things it also affects is the heterogeneity, in the context of how we response to pathogenic or fatal infectious diseases.

NARRATOR: O'Brien's lab had been collecting blood samples for over ten years, looking for some genetic pattern in the way people respond to AIDS. The lab had more than 10,000 samples under analysis.

CHERYL WINKLER: These are viably frozen cells from a patient. They're immortalized lymphocytes. We can take them out any time we want, file them and grow them and get more DNA, if we need to, or do immunological experiments, and from this we're able to virtually any experiments that we would like to do on these cells, which are as viable as if we just took them from the patient.

NARRATOR: Finally, one of those samples revealed an amazing secret. Some people who'd been exposed to H.I.V. but were not infected were missing the gene responsible for the CCR-5 receptor. Without that gene, they produced a defective form of CCR-5 that never got expressed on the surface of their immune cells.

STEPHEN J. O'BRIEN: If you don't make a proper CCR-5 gene, there is no CCR-5 produced on the surface of his T cells or macrophages, and if that happens when they're exposed to H.I.V., it simply doesn't get in, because the doors shut. They absolutely require the CCR-5 molecule in order to enter these cells.

NARRATOR: One of the first samples with the missing CCR-4 gene came from Steve Crohn.

STEVE CROHN: So, for me it's like a key—the virus comes with this, it's looking for a two-holed keyhole. I don't have one of the holes. Period. It's never going to attach to me.

NARRATOR: Steve Crohn's natural immunity to H.I.V. is rare, but it has been found in other people.

STEPHEN J. O'BRIEN: And that, really, it was a natural genetic solution to a fatal retro viral disease, and it was even more alluring because it turned out that patients who had two copies of this virulent ... (inaudible), those that were resistant to infection, were actually quite healthy. Many of them had no immunological disease, or any problems associated with this generic variant. In fact, this genetic variant wasn't a disease; it was a benefit.

DAVID HO, MD: The fact that some individuals can live without CCR-5 suggests that that particular molecule is a good target, since it's dispensable. And so we could develop drugs that would attack CCR-5 without the fear that it was absolutely essential for survival of that host.

NARRATOR: The grand but, so far, elusive payoff of the CCR-5 discover would be an AIDS vaccine.

DAVID HO, MD: We don't know precisely how to use the new understanding to apply to vaccine development today. But, as you can see, vaccine development is generally aimed at protecting the cell from becoming infected, or, generally, protecting the individual from becoming infected, and something that works at the surface in preventing H.I.V. to penetrate into the cell would be crucial. And this knowledge is an important part of that, but how to exploit it is currently unclear.

STEVE CROHN: We don't want to rip this quilt...

NARRATOR: For Steve Crohn, a future free from H.I.V. infection is assured, and his genetic stroke of luck, he hopes, will be part of helping others survive AIDS.

STEVE CROHN: I would like to still be able to make a contribution to whatever research is going out there, if this blood supply, the testing and the research—if I can be involved in that, in some way that makes a contribution, I'm here for that.

NARRATOR: The CCR-5 mutation is not what's protecting Bob Massie. His cellular receptors are normal. What's keeping him healthy is still a mystery.

BOB MASSIE: You know, there's sort of two pieces of this. One is, they want to take what they've learned from studying my immune system and apply it to others, and that's a wonderful piece. I also hope that they eventually figure out why this happened in me, because they still don't really know that. That's the great mystery.

__: Thanks very much. Bye....

NARRATOR: In the course of unraveling that mystery, Bruce Walker has picked up some clues about how to turn ordinary H.I.V. patients into long-term non-progressors.

From studying Massie's immune system, Walker suspects that whatever is keeping him healthy can be traced back to the earliest days of his infection, before the AIDS virus could destroy his helper T cells.

BRUCE WALKER, MD: So, we thought that, actually, we could test that hypothesis, and the way we could test that would be to find somebody who had just become infected, immediately treat them with highly active anti-viral therapy so as to protect these helper cells, as they were being generated, to protect them from becoming infected themselves—

__: —and if you can get somebody through that period and have that immune response developed normally, we think they may have the appropriate tools to move forward and keep the virus under control.

NARRATOR: Walker and Rosenberg came up with a completely novel idea: Find patients who had just been infected and try to rescue their immune systems.

ERIC ROSENBERG, MD: Can I come in? How are you? Good to see you. Do it again, push on my hand. Push. Push....

NARRATOR: In the early years of the epidemic, doctors believed that H.I.V. infected silently, without any symptoms. But studies revealed just the opposite: most people get very sick when first infected, with high fever, sore throat, swollen glands, and other symptoms. But they recover, and they brush it off as a bad case of the 'flu.

These symptoms are called acute retro viral syndrome, the body's reaction to the explosion of H.I.V. in the blood, when it first gains a foothold.

__: AIDS Action Hotline, can I help you?....

NARRATOR: Working with doctors and hotlines across Boston, Walker's team set out to find patients who had just been infected, before they developed anti-bodies, the tell-tale signs of H.I.V. infection, or, even, had an AIDS test.

__: Do you feel you might have been put at risk recently, or this is a check-up?....

NARRATOR: But Eric Rosenberg, moonlighting at the Mass. General Clinic, found their first patient. His name is Mike Burns.

MIKE BURNS: I first came down with a really, really serious fever. I think the temperature was 105, or 104, and I was just burning, burning up.

NARRATOR: Rosenberg was particularly alarmed by an unusual rash on Mike Burns' body.

ERIC ROSENBERG, MD: I was so impressed with his rash that I went to find one of our medical students who was rotation through the walk-in clinic, to look at the rash. And when I got back in the room, Mike actually had new lesions. He had one new lesion on his abdomen that I hadn't seen five minutes before walking out of the room.

NARRATOR: It was a tricky diagnosis. A rash like Mike Burns had is sometimes, but not always, a symptom of acute retro viral syndrome.

BRUCE WALKER, MD: What Eric did was to ask the crucial question, which was, had this person potentially been exposed to somebody who might be H.I.V.-infected, and the answer to that question was in fact yes, he had had unprotected sex with somebody whose H.I.V. status he didn't know, in the preceding two to three weeks.

NARRATOR: It was so early that antibodies to H.I.V. wouldn't have developed yet. A conventional AIDS test would be negative. But if the virus were there, it could be measured.

ERIC ROSENBERG, MD: His viral load, when we initially tested it, was 1.2 million copies per milliliter of blood. The viral load test, in our hospital, only goes up to 750,000 copies, and we actually had to dilute it out to get to the true number of virus, with Mike. So, it was off-scale.

NARRATOR: A series of blood tests left no doubt: the virus had already devastated Mike Burns helper T-cells.

ERIC ROSENBERG, MD: When we did the initial analysis, the first day that we saw him, there were no helper cells present. That in fact made sense to us, because there's so much virus around, that we thought, if any are there they're being infected and eliminated as soon as they are getting generated.

NARRATOR: Walker and his collaborator, Dr. Paul Sacks, put Mike Burns on an aggressive combination of anti-AIDS drugs.

__: Deep breath, and out, and again....

NARRATOR: He is the first patient to take these drugs early in infection, in the hope that they will rescue his helper T-cells and allow his immune system to function in the same way that is keeping Bob Massie healthy.

MIKE BURNS: My understanding is that the hit early hit hard philosophy is one to allow the immune system not to get ravaged in the first place, and by giving my immune system some outside assistance with all these drugs that I have to take, that we are affording by immune system the time to prepare its own defense against the virus.

NARRATOR: Patients like Mike Burns find themselves at the cutting edge of clinical AIDS research, where there are many unanswered questions. Will early drug treatment really save the immune system? Could early use of these drugs make patients resistant to them? And will there be harmful side effects?

MIKE BURNS: Well, I can't worry about it. It's part of the uncertainty that I have to face in life. It's very real, but I don't worry about it, because basically I know that this is the right thing to do, and if I do have some of these other things come up, we'll deal with them one at a time.

NARRATOR: Every step forward in AIDS research is accompanied by risk, and the stakes are never higher than when children are involved.

Twin brother and sister Caroline and Jeffery are three years old. Their adoptive parents are Gail and Allen.

GAIL: It's a good thing we have two chairs, huh, Caroline?...

ALLEN: Jeffery's more of the definitely a man's man: aggressive, and pushy; and Caroline is the little princess of the family.

GAIL: They're both very friendly, active, busy, just get into trouble, if you're not keeping your eye on them all the time.

NARRATOR: On the day Gail and Allen picked the children up for their adoption, they learned that their mother was infected with H.I.V.

GAIL: We had to talk about things like, somebody's got to love them, might as well be us; and I remember tears running down our cheeks in church when we looked at them, because I think we just didn't expect to be able to keep them.

ALLEN: I guess my impression is, we were going to be taking care of some babies for a while, and they probably wouldn't survive into childhood. And so I thought that would be just a sort of small sacrifice for us to do for a few years, and then—

GAIL: We were—I was even wondering if we should be saving up for their funeral.

ALLEN: Yeah.

NARRATOR: Life expectancy for the twins, who soon tested positive for H.I.V., was no better than a couple of years.

JOHN SULLIVAN, MD: There's a very major difference between infants who are infected with H.I.V. and adults. Infants who are affected at birth, most of them would develop symptoms compatible with AIDS in the first two years of life; whereas in an adult, it took approximately ten years.

__: Do you know who works here? This is where Dr. Luzuriaga works.

__: Josie.

__: Josie.

NARRATOR: At the University of Massachusetts Medical Center, the first experimental study, in the country, of aggressive drug therapy for children is designed to help their delicate immune systems fight back.

__: Good boy. Look straight ahead at Mommy...

NARRATOR: The study is modeled after Bruce Walker's research on adult patients in early infection.

__: You were so good....

KATHERINE LUZURIAGA, MD: We had designed this trial precisely with the hypothesis that, with early therapy, we could limit viral replication and preserve children's immune systems, allow them long-term survival, with intact immune systems.

__: All right, Jeffery, let's take a listen here....

NARRATOR: At two months of age, the twins started taking modified doses of the same anti-AIDS drugs given to adults. These drugs had never before been used in children so young.

Gail starts the twins medication first thing in the morning.

GAIL: Well, we start around seven or eight, and we give them a mixture of ice-cream and powder, and then I wait about 45 minutes, an hour, and I gibe them a syringe full of medicine; and then, another half hour, I give them another syringe; and then, around three or four o'clock, we give them another ice-cream medicine with powder; and then, around eight-thirty at night, we do another syringe; at nine-thirty we do another syringe, and at eleven o'clock at night, eleven-thirty, we do another ice cream and powder.

We wake them up, we pick them up out of bed, and we carry them in, and we spoon it into their mouths, then give them some water so their teeth will be somewhat clean, and put them back to bed.

NARRATOR: The hope was that these drugs would keep the virus from destroying the twins' developing immune systems, and it seemed to work well. The children dropped from viral loads of over 400,000 to undetectable levels, until they were just over a year old.

KATHERINE LUZURIAGA, MD: About sixteen months into the therapy, they came in for a routine visit, and we took the bloods, and the guy who does the RNA in our lab called us in, and said, I'm getting a signal.

NARRATOR: Jeffrey's H.I.V. had broken through the drugs, and was starting to multiple. Both twins were immediately switched to a more powerful cocktail; now, their blood is tested every two months.

ALLEN: Breathe in, Jeff, good boy. Good boy.

GAIL: You were so good, Jeff. Great.

ALLEN: Look at Daddy....

NARRATOR: Today, the twins are as healthy as any other children. Recent tests on their blood, using the most sensitive methods available, cannot detect any active virus, and their helper and killer cells are normal.

JOHN SULLIVAN, MD: They're three years and four months of age, and their immune systems are completely normal. If you looked at these children, you would not be able to tell that they were H.I.V.-infected.

NARRATOR: But the children still have H.I.V. genes in their blood cells, and no one knows the long-term effects of the drugs they are taking.

ALLEN: When they first started the treatment, there was no cocktail, there wasn't a prescribed treatment. People were experimenting. And so Jeffery and Caroline had experimentation. And I really feel blessed that they've been as fortunate as they have.

GAIL: It's great that they're at this front line and that they've been this successful. There's lots of ifs. There's still so much unknown. We're right there, with the first group of people, learning that there's still some bad news that we could learn.

NARRATOR: Mike Burns has now been on anti-AIDS drugs for two years, from the very start of his infection.

PAUL E. SAX, MD: He recovered spontaneously from that illness and, also, he's gone on and taken his medicines more successful than almost any other person I know, and has done remarkably well.

PAUL E. SAX, MD: I always ask this trick question: How many doses have you missed in the last couple of weeks?

MIKE BURNS: None. I do not miss doses, you know that.__: You're a model.

NARRATOR: Within a few weeks of starting therapy, Burns' viral load dropped from over one million to below detectable levels. But what is even more exciting for Walker is that catching Burns early seems to have had a significant effect on his helper cells.

BRUCE WALKER, MD: As we continue to treat him, what we saw was the gradual development of a strong helper cell response that, in fact, has been persistent to this day.

NARRATOR: Walker has now studied twenty patients like Burns, and unlike patients who begin therapy later in the course of infection, they have all developed strong immune responses.

BRUCE WALKER, MD: So, this is an absolutely predicable response, if one treats people early. These people then generate the kinds of immune responses that we otherwise see in non-term non-progressors.

NARRATOR: But to advance to the next level, Walker and his team will have to take an even more dramatic, and more risky, step.

BRUCE WALKER, MD: Hi, how you doing? Shall we take a look at some of the stuff?....

BRUCE WALKER, MD: The critical experiment that I think has to be done is to stop therapy on some of these individuals that have these exuberant immune responses, to be able to say whether or not this is enough of an immune response.

NARRATOR: The patient who's volunteered to be the first to stop therapy is John Sarafsky.

JOHN SARAFSKY: From the very first, I was a little bit scared. I mean, I used to work for the Milwaukee AIDS Project, and watching guys pretty much go downhill right before my eyes would flash before, in my memory. But, even now, I'm not really focussing on what possible dangers lie ahead. I'll cross that bridge when I get to it.

NARRATOR: Within weeks of infection, John started taking 14 pills a day.

JOHN SARAFSKY: I took two of these, three times a day; two of these, three times a day; and one of these, twice a day. That's one day, and I did that every day for the past year and a half, now.

__: So, this was pre-therapy?

__: Yes. And this one is ...

NARRATOR: Before Bruce Walker embarked on this experiment, he wanted to make sure that John's immune response was strong. One critical test would show if John's killer cells could recognize and destroy H.I.V. Each one of these wells contains John's killer cells, and H.I.V. A special dye is added, and, if the killer cells are working, they will turn color.

JOIA MUKHERJEE: It's actually very exciting, because you don't know. You do the assay, you put in the cells, and you don't know what you'll see, and at the last step, over a two-day experiment, you put the colorizer on them, and you just kind of sit there and watch. And the first time we saw these in our patients, since we didn't know it takes effect, we were really excited to see them, because each spot represents, theoretically, one H.I.V. recognizing cell.

NARRATOR: The little purple dots reveal that John's killer cells are functioning well.

__: So, it's encouraging, but let's hope it's enough...

__: Right, right...

NARRATOR: But, will they continue to work when the drugs are withdrawn. August, 1998. The time has come for John, and everyone else, to find out.

BRUCE WALKER, MD: Basically, what we need to have you do is sign a consent form, and what this ...

JOHN SARAFSKY: I guess I'm the first one, and I think it's the right way to go. I pretty much trust Eric that, if there are signs of danger, I'll hear about it pretty much, probably pretty much before my body will tell me, and just kind of go with his direction on that one.

NARRATOR: This is a critical moment, the first time that an early intervention patient will stop taking the drugs that have been keeping AIDS at bay. And Walker knows that other labs have tried taking later stage patients off therapy, with disastrous results. Not only did H.I.V. come back in full force, but some patients developed resistance to the medications. That is a distinct risk for John, as well.

__: There's a possibility that when the virus comes back it may be less susceptible to the drugs that we're giving you. We think that will not be the case, but, again, we can't guarantee that, and....

__: I think every physician taking care of a patient feels a personal responsibility. There are sleepless nights when one undertakes some of these things, and one worries about what the outcome is. We obviously try, as hard as we can, to design things in such a way that the risk to patients is absolutely minimal, but one can never be absolutely certain. I mean, one can never guarantee no risk in these sorts of trials.

__: So, you sign right there...

ERIC ROSENBERG, MD: I think that the responsibility is much greater than I ever anticipated, because we have people who are really going into the unknown, and we're asking them to do it. So, I think it has been a big responsibility. But if you go into the unknown with them, and you admit that you don't know what's going to happen, but you think that the—

__: And that's what we're hoping for.


NARRATOR: In the twenty years that he's been infected, Bob Massie has also had to learn to live with risk. His two sons were born before it was clear that H.I.V. could be transmitted between husband and wives, or to infants during birth, but perhaps because Bob's viral load was so low, neither the boys nor their mother were infected. Still, the emotional toll of an incurable disease, the hard reality of AIDS, hangs over him every day.

BOB MASSIE: Doctors don't ever say things with certainty; they use the language of probability. And so, in my case, it's gone from being certain that I would fall ill to possible to unlikely. I would like it to get to the highest degree of certainty possible. I would like somebody to be able to say: You have completely suppressed the virus, you have permanently suppressed the virus. I would like someone to say: There is absolutely zero risk for you and your wife. Now they say "infinitesimally small", but we still practice safe sex, and we still think about it. And it would be very nice to have somebody say: Guess what, you don't have to do that anymore.

NARRATOR: Massie may never have that certainly, but he does have an important role in AIDS research.

__: It's great that it's helpful to other people, and I think that that helps a lot, dealing with the fact that he's not sick, because to just escape and leave everybody behind, in a way, is, I think, harder to deal with. To feel that, at least, your good health isn't just your private victory, it's really something that can help other people, makes it make a lot more sense.

NARRATOR: But the experiment modeled on Bob Massie, with John Sarafsky its first volunteer, got off to a disappointing start.

ERIC ROSENBERG, MD: After John stopped the medication, he felt fine for a number of weeks; his viral load stayed below the limits of detection, for about the first three weeks.

NARRATOR: Then John got strep throat, and it lingered. In the lab, Rosenberg saw his viral load start to climb from 100 to 800, to 1200, and, finally, up to 17,000. He and Walker had to put John back on his heavy dose of drugs.

ERIC ROSENBERG, MD: I think even though, on the outside, he didn't want to admit it, I think that he was scared, and that he very much wanted this to succeed.

NARRATOR: Within two weeks of resuming therapy, John's viral load fell, returning to undetectable levels. That was a good sign. His virus had probably not become resistant to the drugs while he was off them, and, there were signs that his immune system was rallying to fight off H.I.V.: a strong increase in his CD-8 killer T cells.

ERIC ROSENBERG, MD: I think what we have here is not a virus that roared back but a virus that crept back, and so I think we have a suggestion that the immune system actually may have been trying to do something to the virus as it was coming back, and yet there wasn't enough of it, it wasn't effective enough, to really keep things completely suppressed. That's the optimistic view, at this point.

NARRATOR: Carefully, and critically, Walker and Rosenberg will analyze what happened to John; then they will try the same experiment again with other patients, and, perhaps, with him.

MIKE BURNS: It's kind of what we expected to happen but not what we hoped. I figure, well, we'll try it again and if not in this study, there'll be another one, and if it's not me it'll be somebody else. I guess, in a sense, ever bringing us closer to possibly finding a cure, or some way to make this more manageable, maybe like Hepatitis or, hopefully, as minimal as even chicken pox, where you just don't have to worry about it anymore.

NARRATOR: As patients and scientists continue to put themselves on the front lines of AIDS research, no one can really predict what the outcome can be. The goal is turn every AIDS patient into a long-term survivor.

DAVID HO, MD: I think the long-term non-progressives (?) provide hope. They provide hope to the patients that H.I.V. is not universally lethal; they provide hope to the scientists who are working to develop ways to control H.I.V.

ERIC ROSENBERG, MD: As we follow these people longer and longer, and we see more and more examples of individuals now out 20 years, who still have undetectable viral load, I think the likelihood is that some of these people will die of otherwise natural causes and not as a result of their H.I.V. infection.


NARRATOR: Bob Massie, the man who inspired this line of research, gathers with his family and friends, to mark a special occasion: the baptism of his new daughter, Kate. There was some risk that Bob's new wife, Ann, might become infected by getting pregnant, but with Bob's viral load undetectable, the couple decided it was a risk worth taking, and Ann, and Kate, are both fine.

BOB MASSIE: Kathryn Suzanne, I baptize you in the name of the Father and of the Son and of the Holy Spirit. Amen.

BOB MASSIE: I have such a tremendous sense of gratitude when I look at my children. I think, this was a totally unexpected free gift, and what that produces in me is a desire to be worthy of that gift, and to give back to those around me, my family and, more broadly, something that can express how wonderful a gift that is.

NARRATOR: What Massie offers is a clue to solving the mystery of the most dreaded disease of our time. His gift may, someday, turn out to be the key to surviving AIDS.


Surviving AIDS

Written, Produced and Directed by
Elizabeth Arledge

Caren Myers

Associate Producer
Lakshmi Govind

Edward Herrmann

Robert Achs

Paul Bang

Sound Mix
Richard Bock

Online Editor
Ed Ham

Post Production Online Editors
Mark Steele
Spencer Gentry
Jim Deering
Tom Pugh

Assistant Camera
Jerry Risius
Antonio Rossi
John Clemens
Andrew Amorello

John DeSimone
Murdoch Campbell
Michael Guerra

Music by
Michael Whalen

Schwartz/Giunta Inc.

Special Thanks
The NAMES Project, New York City
Massachusetts General Hospital
Aaron Diamond AIDS Research Center
National Cancer Institute
National Institute of Allergies and Infectious Diseases
Princeton University
University of Massachusetts Memorial Medical Center
Brigham and Women's Hospital
AIDS Action Committee, Boston
David Collins and the Estate of Daniel Adams
Dr. Norman L. Letvin, Beth Israel Deaconess Medical Center, Boston
Dr. Robert Gallo, Institute of Human Virology
Dr. Ron Desrosiers, New England Primate Research Center

NOVA Series Graphics
National Ministry of Design

NOVA Theme
Mason Daring
Martin Brody
Michael Whalen

Closed Captioning
The Caption Center

Production Secretaries
Queene Coyne
Linda Callahan

Paul Marotta
Thalassa Skinner
Diane Buxton

Unit Managers
Jessica Maher
Cesar Cabral

Nancy Marshall

Business Manager
Laurie Cahalane

Post Production Assistant
Franziska Blome

Associate Producer
Post Production
Carla Fremlin

Post Production Editor
Rebecca Nieto

Post Production
Mark Geffen

Senior Editor
Program Development
Stephen Lyons

Senior Science Editor
Evan Hadingham

Senior Producer
Coproductions and Acquisitions
Melanie Wallace

Managing Director
Alan Ritsko

Executive Producer
Paula S. Apsell

A NOVA Production by Elizabeth Arledge for WGBH/Boston
© 1999 WGBH Educational Foundation
All rights reserved.


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