- 6/8/2025
What scientists have learned about treating HIV and AIDS from studying people with a natural resistance to the conditions.
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00:00Tonight on NOVA, he is alive against the odds.
00:05He has broken all the rules of people infected with HIV and sparked a new approach to fighting
00:12the disease.
00:14These people are heroes.
00:15We found a group of individuals who are willing to put the greater cause over their own well-being.
00:22Patients like these are on the front lines of bold new research.
00:26Could understanding them be the key to surviving AIDS?
00:52Princeton University, the annual celebration of class reunions.
00:59As far back as the class of 1923, men and women who have survived decades gather to reminisce,
01:06see old friends, and catch up.
01:14But in the class of 78, there's one man no one expected to be here.
01:21The year he graduated, Bob Massey was infected with HIV, the AIDS virus.
01:27A hemophiliac, he got HIV from contaminated blood clotting factor.
01:33At the time, it was a death sentence.
01:36People would say, HIV is a fatal illness, although you can go as long as blank years before you
01:45fall ill.
01:46And the blank was always whatever number it had been for me.
01:51So when people would say, well you can go as long as five years, and I was five years out.
01:57And then you can go as long as seven years, and I was seven years out.
02:01Some people can go as long as ten years, and I was ten years out.
02:03So there's always this sense that I was right sort of at the limit.
02:09But against all odds, Massey, an Episcopalian minister, has stayed completely healthy.
02:16His survival, both a miracle and a mystery, is inspiring a whole new approach to fighting
02:23AIDS.
02:24There are people walking around, and Bob Massey is an example, who have been infected
02:30for almost 20 years, and they're doing incredibly well.
02:34If we can understand what's going on in them, we may be able to take that knowledge
02:39and use it to our benefit in people who presently aren't controlling the virus.
02:48In labs and hospitals across the country, there are bold new experiments going on as researchers
02:54step into the unknown, and patients put their lives on the line.
03:02These adopted twins are infected with HIV.
03:05At two months old, they were the youngest patients ever to be given powerful anti-AIDS drugs.
03:13No one knows what their future will hold.
03:15If we run out of drug therapy, then they might say someday, oh, we shouldn't have used all
03:20our drugs in the beginning.
03:22And if you get to that point, then it's too late.
03:24Other patients are volunteering to stop those same life-saving drugs to see if survival is
03:31possible without them.
03:33These people are heroes.
03:35Whatever information we can glean, we've found a group of individuals who are willing to put
03:41the greater cause potentially over their own well-being.
03:45The courage of a few individuals may open the door for millions of AIDS victims.
03:54And this era of new hope has come not a moment too soon.
04:00With the epidemic well into its second decade, the National AIDS Memorial Quilt has become
04:06an all-too-familiar symbol of the 500,000 Americans and 11 million people worldwide who have succumbed
04:14to AIDS.
04:21What's hard is living with the continuous grief.
04:25You kept losing people every year, six people, seven people.
04:27Last week, a friend of mine's obit was in the paper.
04:31It's not easy when you're losing friends and you're that young and it goes on for such a
04:35long period of time and the only thing you could compare it to would be to be in a war.
04:42The war began when the AIDS virus was discovered in 1984.
04:48It is one of the most formidable enemies science has ever faced.
04:53There are still many, many mysteries about how the body reacts to, protects itself against
05:01or suppresses HIV that are unanswered.
05:06And one of the reasons why they're unanswered is that we're dealing with such a unique virus.
05:10The AIDS virus is unique in part because it attacks the immune system, the very cells
05:18in the body designed to fight off invaders.
05:23Carried through the bloodstream, the virus injects its genes into the immune cells of its victim.
05:30Each infected cell becomes a breeding ground for the deadly HIV virus.
05:35Slowly, but relentlessly, the immune system is destroyed.
05:43Many of these scientists have dedicated the past 15 years to AIDS research, especially the struggle to come up with a protective vaccine.
05:53From the very first moment that the virus was discovered, a vaccine was on people's minds.
05:59And there has been a significant effort to make a vaccine from the very first day.
06:06And I think people thought it would be simple because we'd made vaccines for so many different viruses.
06:13But HIV belongs to a particularly devious family called retroviruses.
06:19There has never been a successful vaccine against a retrovirus.
06:27And many scientists are beginning to believe that a vaccine against AIDS may be impossible to make and too dangerous to test.
06:35If 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.
06:44And then a year goes by and everything's fine.
06:46You say, well, now let's give it to thousands of people, and then you find out that it takes 12 years for all hell to break loose, and then what have you done?
06:55It's been an enormous struggle because the obvious things didn't work, and people got very frustrated by that.
07:03And then the next question was, where do you turn? What's not obvious? What can we do?
07:07It'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.
07:19This lab was the first to show that combinations of antiviral drugs, the AIDS cocktails, could prolong life for many patients, the first real ray of hope in the epidemic.
07:34Now, scientists here are looking for the next breakthrough.
07:39I 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.
07:49What'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.
08:04It was 1994 when Bruce Walker met the patient who would help turn his thinking toward the immune system, Bob Massey.
08:14I 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,
08:32He was so excited and so enthusiastic that it was actually quite charming.
08:41He came in and said, I've been infected for 16 years, but I feel great, I've never taken any drugs.
08:47We thought that was already interesting, but when we got his viral load back, we became incredibly interested.
08:54Lab tests showed that Massey did have antibodies against HIV in his blood, proof he was infected.
09:01But to Walker's surprise, the virus was not multiplying wildly the way it normally did.
09:07What we have here is a viral load assay, which measures the amount of HIV RNA in a patient's blood.
09:14This is a patient that has acute HIV infection, and you can see the yellow color goes all the way down to the final dilution here.
09:21There's a very high amount of virus in this patient's blood, greater than a million copies.
09:26And this last well here is Bob Massey, and he has no yellow color at all and has undetectable viral load.
09:33Without any drugs to control the virus, Massey's natural immune defenses seemed to be holding HIV in check.
09:41An unheard of idea.
09:44Walker and his colleague, Dr. Eric Rosenberg, embarked on a quest to unravel this mystery.
09:51They began at the most basic level of immune response.
09:55Two sets of white blood cells called CD4 helper T cells and CD8 killer T cells.
10:02CD4 helper cells are the first line of defense against any invading virus.
10:11They send chemical signals to the rest of the immune system to begin an attack.
10:16When summoned, CD8 killer cells marshal their forces and eradicate the virus.
10:23But HIV overwhelms the helper cells before they can sound the alarm.
10:29That leaves the killer cells without direction.
10:34Helpless against HIV.
10:38So where is this sample going?
10:43This sample is just going back to the Mass General.
10:48And then there's several different investigators who have experiments that they want to do within our lab.
10:54When Eric Rosenberg and Bruce Walker started analyzing Bob Massey's blood, they discovered something amazing.
11:03His killer cells were doing exactly what they were supposed to do.
11:07We had developed a theory already that killer cells were an important component of an effective immune response.
11:14And so we looked in Bob to see if he had killer cells present.
11:20And what we found was that not only did he have killer cells present, but he had enormous numbers of killer cells.
11:26Once Walker knew that Massey's killer cells were working, the next question was, how was that possible if his helper cells had been destroyed by HIV?
11:38The answer was a complete surprise.
11:41Somehow, Bob Massey's helper cells had escaped the virus and were leading an incredibly strong immune response.
11:49Not only did he have a helper cell response to HIV, but he had a phenomenally large helper cell response.
11:59We were all amazed that we thought that people who were HIV infected just weren't able to mount this type of immune response.
12:08And here was somebody who clearly did, and did it in a way that was never seen before.
12:14Massey was breaking all the rules.
12:19His natural immune defenses were keeping HIV under control.
12:23He's called a long-term non-progressor, and he's not the only one.
12:29About 5% of people infected with HIV are surviving for years without illness.
12:35Understanding these patients could be crucial to saving millions of people who would otherwise die of AIDS.
12:44He's called a long-term non-progressor.
12:48Hello.
12:49How are you?
12:50I'm fine.
12:51Good. Have a seat.
12:52Up until now, the best available therapy for controlling HIV in this country
12:57has been combinations of powerful drugs that stop the virus from multiplying in the body.
13:03All right.
13:04So have you noticed any difference in any of this since I last saw you?
13:07No, I haven't.
13:08The AIDS cocktails have kept many patients alive much longer than would have been imaginable
13:13at the beginning of the epidemic.
13:15But as they are more and more widely used, life-threatening side effects that no one expected are developing,
13:23like diabetes, high blood pressure, and heart disease.
13:28The side effects that we fear the most, obviously, are those kinds of side effects that affect internal organs
13:35and can make people quite ill or cause them to be admitted to the hospital.
13:39And it's possible that long-term side effects of these drugs will turn out to be worse than we anticipated.
13:46And I think patients are extremely aware of that risk.
13:49The cocktail drugs are also enormously expensive, an average of $15,000 a year per patient.
13:58And almost half the patients who try cocktail therapy do not get better.
14:03They develop resistance to the drugs.
14:05Or the drugs simply don't work.
14:08For those of us that take care of patients, we're coming to the unhappy realization
14:13that for many patients these drugs are failing, and we're left without a whole lot of other options.
14:20In the face of this hard reality, the stakes are high as the Mass General Team struggles
14:26to unlock the secrets of Bob Massey's remarkable survival.
14:31I began to see the significance of some of these things when Eric would arrive
14:36and he would jokingly refer to me as the gold standard.
14:39He'd say, I need to draw a little more from the gold standard.
14:43I said at one point, my code name, you know, in the research was 161J.
14:50I learned this.
14:51I thought, well, you know, the irony is that all the other things I'm doing in my life,
14:56books and other activities,
14:59I may end up being more well-known as 161J than anything else.
15:05It is only now, 20 years into the epidemic,
15:10that scientists are grasping the significance of that small group of people
15:15who break the rules of AIDS infection.
15:20One of them is Steve Crone,
15:22a witness to the earliest days of the epidemic in a very personal way.
15:26In January 1978, Jerry Green, my partner, became sick with flu-like symptoms.
15:34And that continued for a while.
15:39Jerry's progression of his disease went on for 15 months,
15:44in which time he suffered a number of debilitating, wasting.
15:49He went blind in one eye.
15:52He had cytomegalovirus.
15:55When he actually passed on March 4, 1982,
15:59there was no such disease as what we call AIDS.
16:03But in fact, Crone's partner was one of the first deaths from AIDS in the U.S.
16:09When the HIV virus was discovered in 1984, Crone worried that he'd been infected.
16:17There was always this underlying suspicion that sooner or later,
16:21it might find its way into my system.
16:23And not because I had lived a very promiscuous lifestyle,
16:29but just because there was something out there that was invisible,
16:32that was transmissible by blood products or human or vaginal juices, whatever,
16:37and that you were exposed.
16:39And there are a lot of people that don't know how to take care of themselves.
16:42But despite repeated exposures to HIV, Steve Crone remained uninfected.
16:49I don't know why I was surviving.
16:52I remember talking about it with somebody at a family party,
16:55and they said, well, why aren't they studying you?
16:57Like, when you look at families and all the children have some malfunction
17:02or bone disorder, some genetic disease or whatever,
17:04they study the child that is not.
17:06And most of the studies were not studying HIV-negative people at all.
17:11Crone volunteered for a study at the Aaron Diamond AIDS Research Center in New York.
17:17Dr. David Ho, a pioneer in anti-AIDS cocktail therapy,
17:22is now looking for new ways to attack HIV by studying people who have resisted infection.
17:28I think we have learned in science that by studying outliers, the extreme result here and there,
17:38you could really learn a great deal about what is happening in the normal situation.
17:43Ho took cells from Steve Crone's blood and flooded them with HIV in test tubes.
17:50He and one other person turned out to have cells that were resistant to HIV infection,
17:59while the cells of others were readily susceptible to HIV infection in the test tube.
18:04And initially, we thought that was a mistake in experimentation,
18:09but upon repeated testing, it gave us the consistent result,
18:14that their cells were resistant to the prevalent strains of HIV-1.
18:21If Ho could figure out why Steve Crone was immune to HIV, the potential was obvious.
18:28A way to protect millions of people against AIDS.
18:32HIV infects the immune system by binding to protein receptors on the surface of CD4 helper cells.
18:45One type of receptor was identified, but it was not enough.
18:49Binding to this receptor alone would not allow HIV to penetrate the cell.
18:55Perhaps a second receptor was needed.
18:59But it would take more than ten years for scientists to find it.
19:06When they finally did, in an explosion of discovery,
19:09five different labs, including David Ho's group in New York,
19:13announced they had isolated the second receptor for HIV, called CCR5.
19:20For HIV to penetrate into a cell,
19:23it needs to have a dual docking mechanism at the surface of the cell.
19:30So HIV will use its own protein, the outer protein,
19:35to bind to two different cellular molecules.
19:39And HIV will bind to CD4 first.
19:42It then changes its structure after binding to CD4,
19:47and therefore the new structure would then bind to CCR5.
19:51And that would cause the two membranes to fuse.
19:54And then HIV then enters the cell.
19:58Since the CCR5 receptor is a protein,
20:03and proteins are produced by genes,
20:06the next question was whether there might be a genetic reason
20:09why some people did not get infected by HIV.
20:14The role of genes in the AIDS epidemic
20:16is the focus of the Laboratory of Genomic Diversity
20:19at the National Cancer Institute.
20:22Human genetics is traditionally thought to involve
20:25hereditary diseases that we inherit from our parents,
20:28but there's something of the order of two or three million genetic differences
20:33between every individual of the human race.
20:37And those differences affect a lot more than hereditary diseases.
20:41They also affect our appearance, our behavior, our immune response,
20:46how quickly our hair grows gray, whether it falls out, and how fat we get.
20:51And one of the things that also affects is the heterogeneity
20:54in the context of how we respond to pathogenic or fatal infectious diseases.
21:01O'Brien's lab had been collecting blood samples for over ten years,
21:06looking for some genetic pattern in the way people respond to AIDS.
21:16The lab has more than 10,000 samples under analysis.
21:20These are reliably frozen cells from a patient.
21:25They're immortalized lymphocytes.
21:27We can take them out any time we want, thaw them and grow them,
21:30and get more DNA if we need to, or do immunological experiments.
21:35And from this we're able to do virtually any experiment that we would like to do
21:39on these cells, which are as viable as if we just took them from the patient.
21:45Finally, one of those samples revealed an amazing secret.
21:49Some people who'd been exposed to HIV but were not infected were missing the gene responsible for the CCR5 receptor.
22:02Without that gene, they produced a defective form of CCR5 that never got expressed on the surface of their immune cells.
22:12If you don't make a proper CCR5 gene, there is no CCR5 produced on the surface of his T cells or macrophages.
22:21And if that happens when they're exposed to HIV, it simply doesn't get in because the door's shut.
22:27They absolutely require the CCR5 molecule in order to enter these cells.
22:32One of the first samples with the missing CCR5 gene came from Steve Crone.
22:40So for me it's like a key, the virus comes with this.
22:43If you're looking for a two-hole keyhole, I don't have one of the holes, period.
22:47It's never going to attach to me.
22:49Steve Crone's natural immunity to HIV is rare, but it has been found in other people.
22:57And that really it was a natural genetic solution to a fatal retroviral disease.
23:05And it was even more alluring because it turned out that patients who had two copies of this variant allele,
23:13those that were resistant to infection, were actually quite healthy.
23:17Many of them had no immunological disease or any problems associated with this genetic variant.
23:24In fact, this genetic variant wasn't a disease, it was a benefit.
23:27The fact that some individuals could live without CCR5 suggests that that particular molecule is a good target since it's dispensable.
23:39And so we could develop drugs that would attack CCR5 without the fear that it was absolutely essential for survival of that host.
23:51The grand but so far elusive payoff of the CCR5 discovery would be an AIDS vaccine.
24:00We don't know precisely how to use the new understanding to apply to vaccine development today.
24:08But as you could see, vaccine development is generally aimed at protecting the cell from becoming infected,
24:15or generally protecting the individual from becoming infected.
24:19And something that works at the surface in preventing HIV to penetrate into the cell would be crucial.
24:26And this knowledge is an important part of that, but how to exploit it is currently unclear.
24:34For Steve Krohn, a future free from HIV infection is assured.
24:41And his genetic stroke of luck, he hopes, will be part of helping others survive AIDS.
24:47I would like to still be able to make a contribution to whatever research is going out there.
24:52If this blood supply, if, you know, the testing and the research, if I can be involved in that in some way that makes a contribution, I'm here for that.
25:05The CCR5 mutation is not what's protecting Bob Massey.
25:28His cellular receptors are normal.
25:31What's keeping him healthy is still a mystery.
25:34You know, there's sort of two pieces of this.
25:44One is they want to take what they've learned from studying my immune system and apply it to others.
25:51And that's a wonderful piece.
25:53I also hope that they eventually figure out why this happened in me, because they still don't really know that.
26:02It's, um, that's the great mystery.
26:06Okay, thanks very much. Bye.
26:10In the course of unraveling that mystery, Bruce Walker has picked up some clues about how to turn ordinary HIV patients into long-term non-progressors.
26:21From studying Massey's immune system, Walker suspects that whatever is keeping him healthy can be traced back to the earliest days of his infection,
26:31before the AIDS virus could destroy his helper T cells.
26:35So we thought that actually we could test that hypothesis.
26:41And the way we could test that would be to find somebody who had just become infected, immediately treat them with highly active antiviral therapy, so as to protect these helper cells as they were being generated, to protect them from becoming infected themselves.
26:57And if you can get somebody through that period and have that immune response develop normally, we think they may have the appropriate tools to move forward and keep the virus under control.
27:09Walker and Rosenberg came up with a completely novel idea.
27:14Find patients who had just been infected and try to rescue their immune systems.
27:19Can I come in? How are you? Good to see you. Do it again. Push on my hand. Push.
27:26In the early years of the epidemic, doctors believed that HIV infected silently, without any symptoms.
27:32I'm just gonna...
27:34But studies revealed just the opposite. Most people get very sick when first infected, with high fever, sore throat, swollen glands, and other symptoms.
27:44But they recover, and they brush it off as a bad case of the flu.
27:49All right. Ready?
27:51These symptoms are called acute retroviral syndrome, the body's reaction to the explosion of HIV in the blood when it first gains a foothold.
28:04Age action hotline. Can I help you?
28:06Working with doctors and hotlines across Boston, Walker's team set out to find patients who had just been infected,
28:13before they developed antibodies, the tell-tale signs of HIV infection, or even had an AIDS test.
28:20Second, do you feel you might have been put at risk recently, or this is a checkup?
28:23Right, right. They love them.
28:26But Eric Rosenberg, moonlighting at the Mass General Clinic, found their first patient.
28:31His name is Mike Burns.
28:34I first came down with a really, really serious fever.
28:40I think the temperature was 105 or 104, and I was just burning, burning up.
28:49Rosenberg was particularly alarmed by an unusual rash on Mike Burns' body.
28:55I was so impressed with his rash that I went to find one of our medical students who was rotating through the walk-in clinic to look at the rash.
29:03And when I got back in the room, Mike actually had new lesions.
29:07He had one new lesion on his abdomen that I hadn't seen five minutes before walking out of the room.
29:13It was a tricky diagnosis.
29:16A rash like Mike Burns had is sometimes, but not always, a symptom of acute retroviral syndrome.
29:23What Eric did was to ask the crucial question, which was,
29:27had this person potentially been exposed to somebody who might be HIV infected?
29:33And the answer to that question was, in fact, yes.
29:35He had had unprotected sex with somebody whose HIV status he didn't know in the preceding two to three weeks.
29:47It was so early that antibodies to HIV wouldn't have developed yet.
29:52A conventional AIDS test would be negative.
29:55But if the virus were there, it could be measured.
29:59His viral load, when we initially tested it, was 1.2 million copies per milliliter of blood.
30:06The viral load test in our hospital only goes up to 750,000 copies,
30:11and we actually had to dilute it out to get to the true number of virus with Mike.
30:16So it was off-scale.
30:19A series of blood tests left no doubt.
30:22The virus had already devastated Mike Burns' helper T cells.
30:27When we did the initial analysis the first day that we saw him,
30:31there were no helper cells present.
30:33That, in fact, made sense to us because there's so much virus around
30:37that we thought, if any are there, they're being infected and eliminated
30:42as soon as they are getting generated.
30:45Walker and his collaborator, Dr. Paul Sachs, put Mike Burns on an aggressive combination of anti-AIDS drugs.
30:54Deep breath. And out. And again.
30:58He is the first patient to take these drugs early in infection,
31:02in the hope that they will rescue his helper T cells
31:05and allow his immune system to function in the same way that is keeping Bob Massey healthy.
31:12My understanding is that the hit early, hit hard philosophy is one to allow the immune system not to get ravaged in the first place.
31:23And by giving my immune system some outside assistance with all these drugs that I have to take,
31:30that we are affording my immune system the time to prepare its own defense against the virus.
31:40Patients like Mike Burns find themselves at the cutting edge of clinical AIDS research,
31:46where there are many unanswered questions.
31:49Will early drug treatment really save the immune system?
31:53Could early use of these drugs make patients resistant to them?
31:57And will there be harmful side effects?
32:01Well, I can't worry about it.
32:03It's part of the uncertainty that I have to face in life.
32:08It's very real.
32:09But I don't worry about it because basically I know that this is the right thing to do.
32:15And if I do have some of these other things come up, we'll deal with them one at a time.
32:22Every step forward in AIDS research is accompanied by risk.
32:27And the stakes are never higher than when children are involved.
32:32Twin brother and sister Caroline and Jeffrey are three years old.
32:38Their adoptive parents are Gail and Alan.
32:41It's a good thing we have two chairs, huh, Caroline?
32:44Jeffrey's more of the definitely a man's man, aggressive and pushy.
32:49And Caroline is the little princess of the family.
32:53Mommy, smash it.
32:56They're both very friendly, active, busy.
33:01Just get into trouble if you're not keeping your eye on them all the time.
33:08On the day Gail and Alan picked the children up for their adoption, they learned that their mother was infected with HIV.
33:16We did talk about things like, you know, somebody's got to love them.
33:20Might as well be us.
33:22And I remember us, tears running down our cheeks in church when we looked at them.
33:28Because I think we just didn't expect to be able to keep them.
33:33I guess my impression is we were going to be taking care of some babies for a while.
33:37And they probably wouldn't survive into childhood.
33:40And so I thought that that would be just a sort of a small sacrifice for us to do for a few years.
33:45And then...
33:46I was even wondering if we should be saving up for their funeral.
33:49Yeah.
33:50Life expectancy for the twins, who soon tested positive for HIV, was no better than a couple of years.
33:59There's a very major difference between infants who are infected with HIV and adults.
34:08Infants who are infected at birth, most of them would develop symptoms compatible with AIDS in the first two years of life.
34:16Whereas in an adult, it took approximately ten years.
34:20You know who works here?
34:21This is where Dr. Lozuriago works.
34:23In Josie.
34:24Yeah.
34:25At the University of Massachusetts Medical Center, the first experimental study in the country of aggressive drug therapy for children
34:34is designed to help their delicate immune systems fight back.
34:38Good boy.
34:42Look straight ahead at mommy.
34:44The study is modeled after Bruce Walker's research on adult patients in early infection.
34:49You were so good.
34:51We had designed this trial precisely with the hypothesis that, with early therapy, we could limit viral replication
35:00and preserve children's immune systems, allow them long-term survival with intact immune systems.
35:07All right, Jeffrey, let's take a listen here.
35:10At two months of age, the twins started taking modified doses of the same anti-AIDS drugs given to adults.
35:16These drugs had never before been used in children so young.
35:25Gail starts the twins' medication first thing in the morning.
35:31Well, we start around seven or eight, and we give them a mixture of ice cream and powder.
35:37And then I wait about 45 minutes an hour, and I give them a syringe full of medicine, and then another half hour, I give them another syringe.
35:50And then around three or four o'clock, we give them another ice cream medicine with powder.
35:55And then around 8.30 at night, we do another syringe.
36:00At 9.30, we do another syringe.
36:02And at 11 o'clock at night, 11.30, we do another ice cream and powder.
36:08We wake them up, we pick them up out of bed, and we carry them in, and we spoon it into their mouths and give them some water so their teeth will be somewhat clean, and put them back to bed.
36:18The hope was that these drugs would keep the virus from destroying the twins' developing immune systems.
36:27And it seemed to work well.
36:29The children dropped from viral loads of over 400,000 to undetectable levels until they were just over a year old.
36:37She's sleeping.
36:38About 16 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.
36:56Jeffrey's HIV had broken through the drugs and was starting to multiply.
37:02Both twins were immediately switched to a more powerful cocktail.
37:06Now, their blood is tested every two months.
37:09Breathe in, Jeff.
37:10Breathe in.
37:11Good boy.
37:12Good boy.
37:13Oh, you are so good, Jeff.
37:16All done, baby.
37:19Great.
37:20All done, baby.
37:21Good boy.
37:22I know, sweetheart.
37:23I'm sorry.
37:24I know, honey.
37:29Today, the twins are as healthy as any other children.
37:36Recent tests on their blood using the most sensitive methods available cannot detect any active virus.
37:43And their helper and killer cells are normal.
37:47They're three years and four months of age, and their immune systems are completely normal.
37:54If you looked at these children, you would not be able to tell that they were HIV infected.
37:59But the children still have HIV genes in their blood cells.
38:04And no one knows the long-term effects of the drugs they are taking.
38:09When they first started the treatment, there was no cocktail.
38:14It wasn't the prescribed treatment.
38:16People were experimenting.
38:17And so Jeffrey and Caroline had experimentation.
38:20And I really feel blessed that they've been as fortunate as they have.
38:25It's great that they're at this front line and that they've been successful.
38:30But there's lots of ifs.
38:31It's still so much unknown.
38:33We're right there with the first group of people learning that there's still some bad news that we could learn.
38:39Mike Burns has now been on anti-AIDS drugs for two years from the very start of his infection.
38:52He recovered spontaneously from that illness.
38:55And also he's gone on and taken his medicines more successfully than almost any other person I know.
39:00And has done remarkably well.
39:02I was asked this trick question.
39:05How many doses have you missed in the last couple of weeks?
39:07I do not miss doses, you know that.
39:10You're a model.
39:11Within a few weeks of starting therapy, Burns' viral load dropped from over one million to below detectable levels.
39:19But what is even more exciting for Walker is that catching Burns early seems to have had a significant effect on his helper cells.
39:27As we continued to treat him, what we saw was the gradual development of a strong helper cell response
39:33that in fact has been persistent to this day.
39:37Walker has now studied 20 patients like Burns.
39:41And unlike patients who begin therapy later in the course of infection, they have all developed strong immune responses.
39:48So this is an absolutely predictable response if one treats people early.
39:55These people then generate the kinds of immune responses that we otherwise see in long-term non-progressors.
40:03But to advance to the next level, Walker and his team will have to take an even more dramatic and more risky step.
40:15Hi. How are you doing?
40:16Should we take a look at some of the stuff?
40:20The critical experiment that I think has to be done is to stop therapy on some of these individuals that have these exuberant immune responses
40:32to be able to say whether or not this is enough of an immune response.
40:39The patient who's volunteered to be the first to stop therapy is John Serefsky.
40:45The very first, I was a little bit scared.
40:50I mean, I used to work for the Milwaukee AIDS Project and watching guys pretty much go downhill right before my eyes would, you know, flash before in my memory.
41:00But even now, I'm not really focusing on what possible dangers lie ahead.
41:06I'll cross that bridge when I get to it.
41:09Within weeks of infection, John started taking 14 pills a day.
41:14I took two of these three times a day.
41:19Two of these three times a day.
41:27And one of these twice a day.
41:30Yeah, that's one day.
41:39And I did that every day for the past year and a half now.
41:45So this was right when he... this was pre-therapy?
41:48Yes.
41:49Okay.
41:50When Bruce Walker embarked on this experiment, he wanted to make sure that John's immune response was strong.
41:55Right.
41:56And...
41:57One critical test would show if John's killer cells could recognize and destroy HIV.
42:03Each one of these wells contains John's killer cells and HIV.
42:09A special dye is added.
42:11And if the killer cells are working, they will turn color.
42:15It's actually very exciting because you don't know.
42:18You do the assay, you put in the cells, and you don't know what you'll see.
42:21And at the last step over a two-day experiment, you put the colorizer on, and then you just kind of sit there and watch.
42:28And the first time we saw these, you know, in our patients, since we didn't know what to expect, we were really excited to see them.
42:35Because each spot represents theoretically one HIV-recognizing cell.
42:41The little purple dots reveal that John's killer cells are functioning well.
42:47So it's encouraging, but let's hope it's enough.
42:52Right, right.
42:53But will they continue to work when the drugs are withdrawn?
42:57Anyway, so let's...
42:59August, 1998.
43:01Again...
43:02The time has come for John and everyone else to find out.
43:06Basically, what we need to have you do is sign a consent form, and what this...
43:11I guess I'm the first one, and I think it's the right way to go.
43:16I 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.
43:26And just kind of go with his direction on that one.
43:33This is a critical moment.
43:35The first time that an early intervention patient will stop taking the drugs that have been keeping AIDS at bay.
43:42And Walker knows that other labs have tried taking later stage patients off therapy with disastrous results.
43:49Not only did HIV come back in full force, but some patients developed resistance to the medications.
43:57That is a distinct risk for John as well.
44:00There's a possibility that when the virus comes back, it may be less susceptible to the drugs that we're giving you.
44:08We think that that will not be the case, but again, we can't guarantee that.
44:15I think every physician taking care of a patient feels a personal responsibility.
44:22There are sleepless nights when one undertakes some of these things and one worries about what the outcome is.
44:31We 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.
44:44I mean, one can never guarantee no risk in these sorts of trials.
44:49So you sign right there.
44:54I 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.
45:06And so I think it has been a big responsibility.
45:09But 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 risk is there's a there's a present risk, but that it's not a risk that is tremendously great.
45:24And the benefit can be huge.
45:26I think that it's one of those things where the benefit can outweigh the risk.
45:30And that's what we're hoping for.
45:32In the 20 years that he's been infected, Bob Massey has also had to learn to live with risk.
45:44His two sons were born before it was clear that HIV could be transmitted between husband and wife or to infants during birth.
45:53But perhaps because Bob's viral load was so low, neither the boys nor their mother were infected.
46:01Still, the emotional toll of an incurable disease, the hard reality of AIDS, hangs over him every day.
46:10Doctors don't ever say things with certainty.
46:14They use the language of probability.
46:16And so in my case, it's gone from being certain that I would fall ill to possible to unlikely.
46:28I would like it to get to the highest degree of certainty possible.
46:34I would like somebody to be able to say, you have completely suppressed the virus.
46:40You have permanently suppressed the virus.
46:43I would like someone to say, there is absolutely zero risk for you and your wife.
46:56Now they say, infinitesimally small.
47:00But we still practice safe sex and we still think about it.
47:06And it would be very nice to have somebody say, guess what, you don't have to do that anymore.
47:13Massey may never have that certainty.
47:15But he does have an important role in AIDS research.
47:19It's great that it's helpful to other people.
47:22And I think that that helps a lot dealing with the fact that he's not sick.
47:28Because to just escape and leave everybody behind in a way is, I think, harder to deal with.
47:36To feel that at least your good health isn't just your private victory.
47:41It's really something that can help other people, makes it make a lot more sense.
47:49But the experiment modeled on Bob Massey, with John Saravsky, its first volunteer, got off to a disappointing start.
47:57After John stopped the medication, he felt fine for a number of weeks.
48:03His viral load stayed below the limits of detection for about the first three weeks.
48:10Then John got strep throat, and it lingered.
48:14In the lab, Rosenberg saw his viral load start to climb from 100 to 800 to 1,200, and finally up to 17,000.
48:24He and Walker had to put John back on his heavy dose of drugs.
48:29I 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.
48:39Within two weeks of resuming therapy, John's viral load fell, returning to undetectable levels.
48:46That was a good sign.
48:48His virus had probably not become resistant to the drugs while he was off them.
48:53And there were signs that his immune system was rallying to fight off HIV.
48:58A strong increase in his CD8 killer T cells.
49:03I think what we have here is not a virus that roared back, but a virus that crept back.
49:08And 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.
49:18And yet there wasn't enough of it. It wasn't effective enough to really keep things completely suppressed.
49:28That's the optimistic view at this point.
49:31Carefully and critically, Walker and Rosenberg will analyze what happened to John.
49:37Then they will try the same experiment again with other patients, and perhaps with him.
49:47It's kind of what we expected to happen, but not what we hoped.
49:51I figure we'll try it again. If not in this study, there'll be another one. If it's not me, it'll be somebody else.
50:00I guess, in a sense, ever bringing us close to possibly finding a cure or some way to make this more manageable.
50:09And maybe, like, hepatitis or hopefully as minimal as even chickenpox, where you just don't have to worry about it any longer.
50:19As patients and scientists continue to put themselves on the front lines of AIDS research, no one can really predict what the outcome will be.
50:28The goal is to turn every AIDS patient into a long-term survivor.
50:34I think the long-term non-progressors provide hope.
50:38They provide hope to the patients that HIV is not universally lethal.
50:45They provide hope to the scientists who are working to develop ways to control HIV.
50:53As we follow these people longer and longer, and we see more and more examples of individuals now out 20 years who still have an undetectable viral load,
51:03I think the likelihood is that some of these people will die of otherwise natural causes and not as a result of their HIV infection.
51:12Bob Massey, 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.
51:35There was some risk that Bob's new wife, Anne, might become infected by getting pregnant.
51:44But with Bob's viral load undetectable, the couple decided it was a risk worth taking.
51:50And Anne and Kate are both fine.
51:54Catherine, Suzanne, I baptize you in the name of the Father, and of the Son, and of the Holy Spirit. Amen.
52:15I have such a tremendous sense of gratitude when I look at my children.
52:30I think this was a totally unexpected free gift.
52:37And what that produces in me is a desire to be worthy of that gift.
52:48And to give back to those around me, my family, and more broadly, something that can express how wonderful a gift that is.
53:03What Massey offers is a clue to solving the mystery of the most dreaded disease of our time.
53:09His gift may someday turn out to be the key to surviving AIDS.
53:27How close are we to an AIDS vaccine?
53:30Get an update on NOVA's website at www.pbs.org.
53:39To order this show for $19.95, plus shipping and handling, call 1-800-255-9424.
54:02And to learn more about how science can solve the mysteries of our world, ask about our many other NOVA videos.
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