This transcript has been edited for clarity.
Michael Saag, MD: Hello. I'm Dr Michael Saag from the University of Alabama at Birmingham, and welcome to Medscape InDiscussion: HIV.
Today we're talking about HIV treatment then and now — how the history of treatment informs our present approach to care. I picked this topic because most folks who are providing care to patients started well after 1990. In fact, many might not have even been born until the 1980s. And there are lessons we learned back then that apply to today's practice. So, I'm going to start with a brief case. A 27-year-old man who has sex with men is referred for his first visit to the clinic after a hospital admission for treatment of HIV-associated cryptococcal meningitis. His CD4 count was 42 cells/μL and his viral load is 127,000 copies/mL. What are the issues we need to address on this first visit? And how does experience from the early days of the epidemic help inform our dialogue with this patient?
Today's guest is Dr Paul Volberding, who is well known to most of our audience as one of the pioneers of HIV research and care dating back to the early 1980s. Paul founded the first dedicated HIV outpatient clinic in the world and is the perfect guest to speak to us on this topic. Paul, welcome.
Paul Volberding, MD: It's good to be here with you today, and I'm honored to be on the program.
Saag: Let's go back to 1981. Where were you, and what were you doing?
Volberding: Mike, as you know, I just finished my training as an oncologist, and I was starting work at San Francisco General Hospital — the safety-net hospital here in San Francisco — closely affiliated with the University of California, San Francisco, where I was a faculty member. But I certainly was not expecting what happened, which is the start of the AIDS epidemic. Literally on my first day I saw my first patient with Kaposi's sarcoma — on July 1, 1981. So, it does take me back.
Saag: Maybe I should have made the case a Kaposi's case.
Volberding: Perhaps, perhaps.
Saag: So how did patients present to you back then? I think we probably should start at around that time, July of ‘81 and all the way through, let's say, the middle of 1983. What was it like?
Volberding: Everything in your case was exactly what we saw, right? Patients with very advanced disease. We didn't know the CD4, we didn't know the viral load at the time. But we knew these people, and I'll say these men, because they were almost all men in the early epidemic, and we pretty quickly learned that they were sick because they had, for some reason, an underlying problem with their immune system. They didn't have much of an immune system. And so they were coming to us with just endless complications of that — infections, cancers, total body wasting — just devastated by this new disease.
Saag: What were your thoughts at the time about what was causing this? I mean it. It was a huge mystery, right?
Volberding: Huge mystery. And I'll confess that at first my focus really was on the patients with cancer, especially the Kaposi's sarcoma, which is by far the most common cancer that we saw in the early epidemic. I tended to think of these patients as having unusual cancers, and, by the way, unusual infections.
Saag: I think we can relate to some of the mystery as we go through COVID-19 right now, that we are experiencing a different pandemic. If we flip it back to February, March of 2020, this weird infection started happening. And at least with COVID, we have tests and we know what causes it. In your situation, you were just dealing with an onslaught of young men flooding your clinic and you having to deal with it. That is almost unimaginable to most of us who are practicing today.
Volberding: Right. And a little bit later, after the first early phase of the AIDS epidemic, people were angry because they felt — appropriately so in many cases — that not enough was being done and they were certainly angry because nothing was available to help to help them. But I do remember at one point that Marcus Conant, who is one of my colleagues here, in the early epidemic said, in talking about how the federal government was slow in responding, "You know, maybe when we've had 1000 cases, they'll start to respond." And he meant, I think, probably 1000 cases in the world at a time when we just had a handful, and as you know, the numbers quickly became astounding for HIV. They doubled every 6 months or so. And so even though it never got to the range of today's pandemic in terms of absolute numbers, and it took a longer time to do it, the numbers were huge and the impact on us as providers and on healthcare systems was really unprecedented.
Saag: One of the things that you worked on, in particular, your colleague Donald Abrams, worked on lymphadenopathy, and this is particularly related to hem-onc because these people were showing up with large lymph nodes. You thought it might be some form of lymphoma. It wasn't. Tell me how you all dealt with that.
Volberding: In the very first days of the epidemic, we didn't have a test. As you well remember, all we saw was the advanced manifestations, the opportunistic infections, the cancers. And we didn't know: Is this the disease or is there something bigger than that? There were hints that maybe there was a prodrome, that people were on their way to developing AIDS. In the first really strong sense we had of that was the lymphadenopathy syndrome that Donald Abrams studied so amazingly well. He was studying that even before our first AIDS cases were diagnosed. So, it turned out that, in fact, all of those people were infected with HIV, of course. It also turned out that essentially all of them would go on to develop AIDS because by the time you got any physical manifestation of the underlying HIV disease, you were on your way to die. That was an early and loud warning signal.
Saag: And when you talk to the patient, you're basically saying, "Well, how are you feeling today?" Because the future didn't look terribly bright.
Volberding: The patients, often patients with one or two Kaposi's lesions, would say, "Yeah, doc, I know this is bad.” They'd been reading the press, but they would say, "But I'm going to beat it." And these were young people; they had every intention of living another 40, 50 years. At one point, you'd say, "Of course. That's wonderful. Let's work together to help you do that." On the other hand, you said in the back of your head, No one beats this. This is something that is beyond us. So there was the tension between what we hoped for, both us and our patients, and what we fully expected to happen.
Saag: So you and your colleagues were dealing with this every day. Let's fast-forward. '83, you're swamped. You're overwhelmed. How did you guys manage yourselves? How did you get up every day to walk into clinic to see yet another onslaught of people who had this hopeless new disease, of which there was no cause and just the numbers kept going up and people kept dying? How did you guys take care of yourselves?
Volberding: I thought of that in today's pandemic with stories of these poor people not getting a lot of media attention or fame or anything else. They're just slogging it out. They're going to work. They're working hard, they're working long, they're covering shifts. And for us, I think there was exhaustion. It wasn't as physical as I think we see today with the COVID shift work and all that. But certainly, it was mental. These people, the patients, were our age. And in the case of our many gay providers, shared a lot of life experiences with patients, which made it very hard to separate emotionally from our patient care. And so it took a toll, especially as the numbers increased and before we had any kind of treatment. At one point, I found that my staff were all kind of at each other's throats. People who normally behaved well were behaving poorly. People were yelling in the hallways. And it wasn't that they'd become bad people. They were just overwhelmed. And so we dealt with it by bringing in a team of therapists to really help us learn how to cope. That helped a lot, and I think other places probably used similar techniques, but it was not easy.
Saag: Fast-forward to March or April of '83. The virus gets discovered. A test gets developed in 1985, so you can start tracking this, and treatment arrives on the scene in roughly 1985-86 in the form of clinical trials of AZT. I know you guys were pioneers in those early days of AZT. What was that like for you and for the patients to go on these clinical trials?
Volberding: It's interesting. I use the word a lot, but it was interesting and reminded me a little bit of what I knew about the development of oncology and where we started having occasional drugs before my time, but that never cure the disease. But it had a glimmer of hope, and that's what AZT was. I think even at the time, it certainly wasn't curing anyone, but it was the first really legitimate drug that seemed to be doing something. And people were really of mixed feelings about it. People were afraid of its side effects, which we soon learned were considerable, not life threatening, but it did have side effects. It was inconvenient, had to be taken, at first, every 4 hours around the clock. On the other hand, it was the only thing that we had that offered real hope. People hated the idea of placebo-controlled trials, and yet they clamored to get into them because they were the only option.
Saag: Right. So, for the audience who didn't live through that time, there was a placebo-controlled study that was stopped by a data safety monitoring board because by 6 months, a huge divergence in terms of mortality was seen in those who got placebo vs those who got AZT. They opened it up, they gave everyone AZT who was on the study, and there was hope: "We can finally do something. We're tired of watching our friends die." You had experienced the same thing, I'm sure.
Volberding: Oh, absolutely. Having even a single somewhat active drug really made all the difference in the world. And again, it was before we had viral load. We didn't know how to follow the response to the treatment, but we had treatment which, for us and our patients, made a huge difference.
Saag: So for those who weren't around at the time that viral load was developed, that was something we were fortunate to stumble onto in collaboration with some folks at Gene Labs. Basically, PCR was around since the mid-1980s, but it couldn't be quantified. And this group of gene labs figured out how to quantify it. We did some studies with that. It was just striking how the amount of virus in the bloodstream, as measured by the viral load, correlated to progression of disease and stage of disease. But more importantly, when you started therapies, even AZT, you could see about a tenfold or 1-log drop in virus, which was unprecedented in terms of being able to watch activity. And the big change that happened is in clinical trials, instead of waiting for body counts — which was grotesque in terms of "did drug A work better than drug B?" — now we could look in a matter of just a couple of weeks and say, yes, this one's working or no, that one's not. And that led to the so-called HAART revolution, where we realized that combination therapy worked. And as you said, 1996 — when it all came together and we said, "Wow, we're making a big difference not only in terms of getting the virus under control, but people aren't dying in any form or fashion like they used to." How did that play with you personally at that moment?
Volberding: So, remember that when we started seeing our AIDS patients, PCR hadn't been developed. Unbelievable. The technology that we now treat as every-day — you know, how people do at-home PCR tests — PCR hadn't even been developed. And when it was, and especially when we had a quantitation to it and applying it to HIV, that made all the difference in the world. The way you looked at the reduction in viral load — just statistically, going from, as you were saying, a 1-log reduction, which was remarkable — you could really see it to thinking about the fraction of people who became undetectable by PCR, which really allowed us to go, "Oh, this is more than just an antiviral. This is really remarkable." And all of that was based on this technology that we didn't have until about the mid-'90s. And interestingly, it was almost simultaneous with the development of effective treatments. So, thank God, we had both. We had the test, which allowed us to know that the treatments were effective. Otherwise, I'm afraid it may have taken us a lot longer to know that these combinations were; we may have abandoned them altogether because they were cumbersome, they had complications. But with the combination of the drugs and the viral load, that was really — together — the revolution.
Saag: So, we learned that complete suppression of replication prevented resistance, allowed people to live a relatively normal life span. And that's kind of where we are today with much better drugs, fewer side effects, convenient regimens, one pill once a day. How are you taking that information and using it as you take care of patients today?
Volberding: Well, it's the amazing story from the early days of combination therapy to more recently, and it's not even that recent anymore, right? We've had a single-pill combination for a number of years now. But today, we have our choice of two-, three-, four-drug combinations, all in one pill taken once a day and typically with essentially no side effects. I mean, there are side effects, but it's not like the early days of combination therapy when people had substantial side effects. These pills are easy to take, and so I think it's easier to talk to patients about treatment. I don't find the same level of resistance to treatment that we saw in the early days of combination therapy. Fortunately, there hasn't been a public disinformation campaign, the way we see with COVID about science. Our patients tend to believe us when we say that a treatment is good, and it's really only the patients who have a lifestyle that is often so chaotic that even something as simple as one pill once a day is beyond their ability. But it's a different world. And when we start therapy in a person, we can essentially say, "I'm going to prescribe a drug. If you take it, if you're able to take it as it's prescribed, your virus will become not effective, or you will not become drug resistant, and you have a very real chance of leading a normal span." We think a lot about HIV cure, but we're off roughly close to that in terms of our treatments.
Saag: It's a functional cure of sorts. The term is used in a different way, but people can live a normal life span and, oh by the way, not transmit to others. I found that you're right; you offer this therapy to people and they mostly willingly take it. I've had on occasion a few people who push back and say, "Nah, man, I don't want to be treated for this." Are there any tips you have that you use, especially drawing back on your past experience, as you counsel someone to try to convince them that this is a good idea?
Volberding: I think giving people the space to make their own decision is really important. That's kind of always true in medicine. We're never going to force people to be treated if they don't want to be treated. But we're often seeing them in the context of a clinic that's specializing in HIV care. So they have a chance to see other people, talk to other people. There are, fortunately, enough organizations that really cater to people with HIV that provide good information. So, in most cases, it doesn't take long for people to come around. I've had patients over recent years who don't agree to be treated until they develop something like thrush. That's pretty advanced. Your CD4 counts are probably below 200. Until they really see something, some physical evidence of disease, they're reluctant. But I think even that's getting to be rare.
Saag: One thing that I've done on occasion is to just say, "Look at me and my gray hair." I've done this for a while, and just to describe what we've been talking about, about how awful the old days were and what a miracle it is that we have these new drugs available to us. Looking around the clinic at how many people are doing well and how in our routine visits for those folks, we rarely even talk about HIV; we're talking about hypertension or diabetes, and we don't talk about resistance and all the stuff we're used to. So, it's really something to celebrate.
Let's return to the case, and let's put this guy in the room with you right now. You've already alluded to this somewhat, but what would you say to him? You're going to offer this treatment. You're going to tell him about living a normal life span, the importance of taking it once a day, and the ability — once it's successful — not to transmit the virus to others. What are some of the things that you would tell this patient on this first visit?
Volberding: I think today is not that different from in the early days of the epidemic. Somebody on a first visit, newly diagnosed, especially somebody with severe advanced HIV disease, is going to be scared to death. And so I would really respect that. Just as with my cancer patients, I would not try to load on too much in that first visit. I would expect that he's not really hearing everything I'm saying. So I keep it simple, but I would start pointing out the reasons for hope: While I understand his anxiety, his fear, we have something to do to take care of the disease. You know, we talk a lot these days about rapid initiation of antiretroviral therapy, and I'm a believer in it. But with somebody like this, I'm going to give him a little bit of space. It doesn't matter to me that he has to be treated the first day I see him. Much more important is that he comes to a point where he understands that this is a chronic, manageable disease and hopefully quickly decides to start treatment. And that gives me the space to really talk about the different treatment options. There are a number of them that might appeal differently to different people. So, it's a wonderful world in that sense.
Saag: And the other thing that we've sort of alluded to, but I think it's worth bringing out directly and you just talked about it, is the psychological aspect of dealing with this new diagnosis and, as you said, giving them space. What's also important is to find out if there's some one person they can share this with — this new diagnosis — and not go through it alone. How do you approach that with your patients?
Volberding: Well, I'm only sorry that this is a podcast and not a video, because you can't see me nodding my head so vigorously, but I couldn't agree more. I mean, I think most people have someone else. Most people have someone else that they trust that they are close to. The combination of two people is much more potent than two individuals, right? I think that dynamic can be very helpful. Questions arise, and it's helpful for any of us to talk to someone else. If it is a person that's really quite isolated, fortunately now there are organizations in many cities that can help with this, and there are online resources. Again, in the early epidemic, there was no online. Now we have a lot of options, both for support and for information.
Saag: For somebody who gets this diagnosis, it's a total shock. That's the same as it was back in the early 1980s. The difference is that it's not actually the death sentence that it pretty much was in the '80s. We know that we can get people to a place where they can live with HIV very, very well. And that's what our goal is. We just didn't have that back in the day. But the stigma that can come with this, the psychological shock of it having to deal with this, is something they need to talk to others about.
Volberding: My guess, Mike, is that you see this more in your part of the country than we do here in San Francisco — that the sense of stigma is still, I think unfortunately, very real. And we see people, but we hear of people that fear the stigma so much that they don't even want to be tested for HIV, much less have to come to the point where they're considering treatment. So there's still a lot of ground to cover there. And I think that still might prove to be some of the most difficult ground that we face.
Saag: The time has moved along quickly, as I knew it would. Let's wrap up with one final question for you. What's the one thing, based on your years of experience, that you want to pass along to the practitioners who are listening, that might be useful to them?
Volberding: I think one lesson is how important it is that we have the ability to make decisions based on information. When we're in the dark, we're really in the dark; in the early epidemic when we didn't know what was going on, it was really hard. The more we can shed light on a situation — the disease and infection — by good science and good information, we're just in so much more of an empowered position. And I think the support that we saw for science with HIV is something that's as important now with any new diseases as it was with that. I think that's really one of the most important things.
Saag: Thank you so much, Paul, for your wisdom and insight and your ability to very clearly express what it was like back in the early '80s. The tough times that you went through personally, all of your staff and your team, and, of course, your patients, as they suffered through this new exploding epidemic of HIV/AIDS. And then the transition to hope, where we could actually realize how the science came together in a way that not only gave us better diagnostics, like viral load, that made it easier to stage people, but also to see how treatments were working, and especially when they were failing. And now we're at a day where we can keep assuming that the patients take their medications regularly, have people live normal lifespans, and not transmit to others. It's really been miraculous.
Volberding: It actually has been, yeah.
Saag: Forty-one years.
Volberding: And let me just add, Mike, at the end of this, the group of people that were affected that you didn't mention. I'm sure you agree it's the families — the families of our patients but also our families. In the early epidemic, you and I and many others creating our families, they suffered through this with us as families do today. And so it's kind of a tribute to them as well.
Saag: Absolutely. That's a great point. Well, thank you again for joining us. This has been spectacular, and I can't thank you enough. Our guest today has been Dr Paul Volberding from the University of California at San Francisco and the San Francisco General Hospital. We'll sign off here.
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Cite this: HIV Treatment Then and Now: How Our Past Informs Our Present - Medscape - Mar 01, 2022.