Dr. John G. Bartlett looks back on AIDS: A 30-year perspective

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Dr. John G. Bartlett when he first joined Johns Hopkins in 1980.

HIV specialist and leading infectious diseases physician John G. Bartlett, MD, doesn’t mince words when you ask him about what his AIDS patients faced in the early days of the epidemic.

“They were the scourge of society – people didn’t like them because they were either gay or injection drug users, and there was a fear of contagion, that if you were in the same room with someone with AIDS you might get AIDS… They had diarrhea and dementia and wasting. It was an awful way to die. And besides that, everyone around you hated you. Can you imagine living to die that way?”

Dr. Bartlett became a ray of hope for people living with HIV/AIDS. He directed some of the first clinical trials of new treatments that prevent HIV from replicating, and pioneered the development of dedicated in-patient and out-patient medical care for HIV-infected patients. A Stanhope Bayne Professor of Medicine in the Division of Infectious Diseases (ID) at Johns Hopkins University, Dr. Bartlett served as chief of ID at the school for 26 years, stepping down in June of 2006. He co-chaired the national committee that drafted the first and all subsequent treatment guidelines for HIV-infected patients from the Centers for Disease Control and Prevention (CDC).  Dr. Bartlett was recently elected to serve as co-chair of the Forum for Collaborative HIV Research’s Executive Committee, and is a former president of the Infectious Diseases Society of America and member of the HIV Medicine Association Board of Directors.

In our third interview in a Science Speaks series commemorating 30 years of AIDS, Dr. Bartlett speaks frankly about hiding his treatment of AIDS patients from hospital administrators in the early ‘80s, key scientific breakthroughs over the years, and his views on the President’s Emergency Plan for AIDS Relief (PEPFAR) program moving forward.

Do you remember hearing about the first cases of what would become known as HIV/AIDS? What were you doing at that time?
I came to Hopkins in 1980 so I was sort of new here, and there was no ID Division so it had to be built from scratch. I had heard about it because I had talked to one of the people that was involved in the cases in Los Angeles. I called in the context of a patient I saw who actually had the disease here in Baltimore, but I couldn’t understand why because it was a woman. She had no reason to have pneumocystis pneumonia – she was an injection drug user (IDU).

So I called LA to ask what’s going on – and the answer was, “This is an epidemic.” And they said, “So it’s a gay man.” And I said “No, it’s a woman.” It was an awkward conversation! They just expected it to be a gay man. At that time it was known as GRID, gay-related immune deficiency. I was puzzled by it, we all were, and all I could do was treat her for the pneumonia and she died.

So when I saw the Morbidity and Mortality Weekly Report (MMWR) I was not surprised by it, but a lot of us were totally puzzled because we’d really dealt with pneumocystis pneumonia extensively among cancer patients and others, yet there was no reason for these otherwise healthy people to have it.

So I stored it in the back of my mind, it wasn’t something I was interested in specifically. Then after the report from MMWR, an epidemiologist and a close friend of mine, Frank Polk, came to me on one of our regular Saturday morning powwows, and said he thought the GRID disease was very important and that he was going to change his career in order to study it. I told him, “This is a bad decision on your part. There’s a modest epidemic, seven people have died, and you’re changing a very productive career to do that?” And he said, “This is going to be a big one.”

Polk led the first big studies of AIDS in the U.S. The oldest one in the history of AIDS is the Multi-Center AIDS Cohort (MAC) Study from 1984, which studied gay men with the disease and gay men without, prospectively. And then Polk set up the ALIVE study involving IDUs, and the Red Cross study of blood transfusion-associated HIV infection. He set those all up in the early 1980s and he had a really great career here at Hopkins. He died of a brain tumor in 1988. He was clearly a very great leader in the field.

But that was how I got started. It was really working with him. And he said somewhere along the line, “I’ve got this huge study of gay men with HIV infection in Baltimore and you need to set up a clinic to care of them.” So we started the Moore Clinic, the AIDS clinic at Hopkins, in 1984. And we hid it. We hid it from the hospital administration because the disease had such a horrible connotation associated with it. So we called it an ID clinic, but it was devoted to AIDS.

Dr. John Bartlett lecturing on antimicrobial resistance in 2010.

How long did it take for them to figure out what was going on?
It was interesting. The president of the hospital at the time was Bob Heyssel, a hematologist. I remember in 1985 or ‘86 he went to New York for a meeting and he came back and said, “I need to meet with you. I’ve been to New York – there’s this virus going around and we really need to do something about it.” And I said, “Well, we’re already doing something about it. We’ve had this clinic for about two years…”

Baltimore always had a lot of cases, because of IDU and the epidemic of heroin use in the city. We had a pretty large clinic at the very beginning.

“I want you to build a program,” he said. So I wrote a grant out and gave it to him a month or so later. After Bob read it he said, “I like everything in your plan except you didn’t charge enough – you’re going to need three times as much money as you have in your plan.” And he funded it – then we got our AIDS ward at Hopkins in 1986. That was the 2nd AIDS ward in the U.S.; the first was San Francisco General.  SF really got a jump start on this; they had a lot of gay men and a lot of morbidity, really just awful.

What have been the most memorable moments for you in the epidemic?
Along the line the epidemic had some really seminal events. The obvious were the first cases in 1981, the discovery of the virus that causes AIDS in 1983, the test that permitted them to test the blood supply and cases in patients in 1985. Those were the seminal events in the early part of the AIDS era.

Then it was the AZT trial. In 1985 or ‘86, they randomized patients to get AZT or placebo. It was a pristine trial design, placebo controlled, and it was not a huge number of patients that participated in the trial, but it was a well-done study. The first time the data monitoring board looked at the un-blinded data in September 1986 there were 19 deaths in the placebo arm and one death in the group that got AZT. And these patients were getting a very high dose and had to take it every four hours – they had to get up in the middle of the night to take it. But it was a shock around the world when the results came out. That’s how we got our first drug. It was really important because it told the world that you could do something to combat this virus. It turned out to be not much of a victory, because in retrospect you only had an average of about 6 months more life –patients got resistance and it made them sick as hell. But in 1987 it got FDA approved, at record speed, because there was this desperate need for an AIDS drug.

In 1994, the 076 study was published and showed that AZT prevented perinatal transmission, or pregnant women transmitting it to newborns. I would have to say that if you were to go to any care provider, any place in the world, the darkest reaches of Africa, and say “076” they know exactly what you’re talking about. That’s a study that’s known all across the world by its name – 076. That was a big deal – it was quickly embraced by medicine and then the infections in the U.S. among newborns went down to almost nothing.

The next seminal event was 1996 – which was the introduction of what we now call HAART or highly active antiretroviral therapy. Every year in the summer we go to the International AIDS Conference, this time it was in Vancouver, and that was probably the most dramatic conference in the history of AIDS because you went into the conference knowing that everyone who had AIDS was going to die, and you came out knowing that everyone was going to live. And that doesn’t happen in medicine.

At the same meeting they presented the results of a big trial involving indinivir, one of the first protease inhibitors. It was presented by Trip Gullick – published in The New England Journal of Medicine after that.

One arm received indinivir boosted with ritonivir; a second arm got AZT and 3TC, a combination of two nucleosides used most commonly at the time; and the third arm received the boosted indinivir and AZT 3TC. The third group that got all three had an 80 percent achievement of the goal, which is to have no detectable virus with less than 50 copies per milliter at 48 weeks. And that’s been the definition of treatment success ever since. The real victory was the combo of all three of them, what established what we now call triple therapy. That’s what we now use.

You can’t name another major disease in the last fifty years where there has been that kind of achievement. Our clinic was a place people came to die. They all died, they all knew they were going to die. It was a universally fatal disease, until 1996. It changed everything.

David Ho made the statement at the time that if we gave that kind of therapy to people with the disease they would be free of the disease in three years. Now he may wish he hadn’t said that, but he also said “Hit hard and hit early” – that turned out to be prophetic. He was the man of the year in Time Magazine, and everyone thought this was a done deal. But at that point we didn’t yet know about the latent pool where the virus hides, we just knew about virus in the blood. 

Indinivir subsequently has gone almost out of existence. It turned out to be quite toxic, but now there are 24 or 25 different drugs in the armamentarium of HIV drugs.

Around the advent of PEPFAR, many people discounted the idea that it was feasible to treat people with HIV in Africa. What was your experience at the time with that mentality?
A variety of people take credit for selling PEPFAR to President George W. Bush. I think Tony Fauci might have been the one that really got it going. He had a successful career at the National Institute of Allergy and Infectious Disease, and when he got that MMWR it changed his career. If I had to pick, I would say Tony was clearly one of the early heroes. When he made those commitments to study AIDS at the beginning, people thought he was nuts. There were a host of other diseases that were responsible for causing far more deaths in the world and the U.S. But he stuck to it. He got heavy funding for AIDS research, and he devoted much of his own research to it.

President Bush was a big deal – he was the one that heard the story that all these people in Africa are dying of AIDS. Clinton brought attention to AIDS in other areas of world. He put it on the radar screen that it threatened the economic, social and political stability of the world because it’s such a galloping disease that killed young adults. But George W. Bush was the one that said, when he heard the story, “You tell me we can do this. We’ve got to do it. It’s a no-brainer.” And back in 2004 he established PEPFAR with $15 billion. It was really a compassionate thing that was necessary to do to stop this carnage in Africa. If you looked at the numbers and the way it was growing, you had the feeling that much of the middle class in most of the world was going to be gone.

What do you think the implications are for the HPTN 052 Study – which shows that early treatment of people living with HIV can limit the spread of the disease to an HIV-negative partner my more than 96 percent – for global and domestic policy and practice?
If I had to say, what’s striking about 052 is, why did it take so damn long to do something that is so painfully obvious? My take on it is it’s spectacular for the field because it nails the concept. And nobody has to talk in the abstract anymore. We could have predicted it, but it’s great to have the data. And I think for a lot of people that really means, if you can get no detectable virus with treatment, that equals prevention.

There’s this big study being done called HPTN 065 TLC in Washington, DC. They’re trying to test as many people in DC as they can that might have HIV, treat everybody that tests positive and show that testing and treating will decrease the epidemic. And that’s sort of the spin off of Mike Cohen’s 052 study. If everyone in DC is treated, will there be any new cases of HIV in DC? Could you stop that epidemic? And this is very, very important right now because no matter how hard we try we can’t seem to stifle the epidemic of new cases. There are 52,000 new cases per year in U.S., but in Africa there are three new cases for every one person with HIV we treat. So we’re playing catch up. It will be interesting, but the concept of treating everyone up front will be very costly.

Tell me about the work you’ve done in Ethiopia.
I go to Ethiopia as part of an NIH grant with Dr. Andrea Ruff as the principal investigator, the main purpose of which is to get access to drugs and treatment for people with HIV; it’s part of the PEPFAR program. And so I went there at the beginning to help build that program.

Since then, I’ve gone back and forth many times. I go to the clinics, give the lectures, go on rounds at the Black Lion hospital, and teach, much as I do here. But now the PEPFAR mission in Ethiopia and in the rest of the world has evolved from the original goal, which was largely focused on AIDS, and now there is much more attention on other health issues, especially building a healthcare infrastructure that deals with all facets of healthcare including TB and malaria.

There is a lot of TB in Ethiopia. TB is a neglected disease – it kills just as many as AIDS, and the last new drug for TB was introduced 50 years ago, if you can believe that.

All of a sudden now there is great interest in TB; TB is now a big deal in the U.S. at NIH. I think AIDS got us there, it got us into Africa and it got us to look at things other than AIDS. But then it went further. What I think the Obama Administration has said is, “We really need to build a system of care in Africa so it can be a self-sustained program, because we can’t necessarily keep funding it forever. They should be self-sufficient in this.”

In Africa there was no system of chronic care, there was only acute care. If you had diabetes or something like that it was very hard to get care. Now there’s a need to establish an infrastructure of medicine with medical education and clinics that would do chronic care for things like HIV infection. Now when I go to Ethiopia I talk about all infectious diseases – everything that I talk about here in the U.S.

Fifty to sixty percent of deaths in Ethiopia are due to infectious diseases. That’s their big challenge.

Right now we are still not ahead of the curve for HIV. If there are three new infections for every person we treat, we’ll never win if there are more deaths than people treated. It’s going to be hard to deliver enough drugs and build that self-sustaining infrastructure for chronic care. But I think Mike Cohen’s 052 Study has lit that fire – the more people you treat, the more you deal with the epidemic.

What’s going to be big moving forward? What do we need to do to end this pandemic?
We’ve got to be able to test everybody. Half of people in the U.S. have never been tested. We’ve got to find the people that have the infection, and then we’ve got to get them in care and keep them in care. In Washington, DC, they’re actually paying people to get tested, paying them to get treatment. There’s an economic incentive. I think that works very well. We’ve done some of that here in Baltimore, but it is controversial.

What the plan needs to be is to treat as many people as we can and get ahead of the curve. That’s our big challenge right now. The World Health Organization probably said it right – as long as we’re behind curve, as long as there are more new cases than we can treat, then we are always going to have an epidemic that is growing. We can’t have that. We’ve got to somehow stop the epidemic. So the prevention part of it has become maybe the highest priority in the AIDS field. It’s interesting that here we are, the disease was described in 1981, and here we are in 2011 and we’re talking seriously about prevention. That’s pretty humbling. It’s not that we didn’t think about prevention, we’ve always thought about it, but we’ve never had the tools to work with it successfully. We’ve got the tools now. Our next big challenge is to prevent and/or cure. I’m optimistic that we’ll be able to do both.

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