Treating HIV Is Rarely an Emergency
An Interview With Joseph Sonnabend
Dr. Joseph Sonnabend was one of the earliest AIDS clinicians and researchers. He helped introduce the concept of safer sex and was a pioneer in establishing community-based research. He was mentor to many of the first generation of AIDS activists and is famous among patients for being the first doctor who treated them as equals. He recently retired from medical practice in New York and now lives in London.
BH: When you hear the term "salvage therapy," what does that mean to you?
JS: I'm personally distant from it in the sense that it's not an issue that has arisen much in my years of practice. I haven't taken a great deal of interest when there have been meetings or sessions on salvage therapy. I have not taken a great deal of interest because I have only rarely been in the situation where I have had patients whom I've started on therapy who have reached the point of requiring salvage therapy.
I've had patients in clinics and people who've come to me from other doctors, so I've had a few of those patients whose treatment options were very limited, but not many. I really can not recall ever having prescribed T-20, for example. I would have if that situation had ever arisen, but it never has. And I've had thousands of patients. And I'm obviously speaking about patients who started therapy during the protease inhibitor era.
I know that treatment can fail, of course. Certainly I've had failures; one patient just wasn't very mentally reachable; another decided she had found another source of salvation. But by and large, they've done really well.
So I've had to think about why I have been so fortunate. It's partly what I have done, and partly what I haven't done, and another part is the kind of practice I've had: a private practice consisting largely of gay men; patients who are better educated; better motivated, maybe; more knowledgeable about the medications and probably more likely to stick to their drugs. So, credit goes there, but on the other hand I know there are many patients of this kind who really are in trouble.
BH: This is surprising since the conventional wisdom says that if you've been treating gay men for a long period of time, they've gone through a lot of different regimens and they end up resistant to everything. So what was different about the way you were treating them?
JS: It may have to do with what I have not done. First, I have not started people on treatment too early. When the original version of the treatment guidelines came out I thought they were very, very wrong headed. I wrote a response -- I suggested that the way we resolve clinical uncertainly is by doing proper trials, not by issuing guidelines. HIV medicine had already moved somewhat away from the traditional way of trying to find answers by doing many well-designed trials and was moving toward relying on the consensus of a panel of experts.
I thought they seemed to be gazing into a crystal ball as to the long-term effects of therapy. If these drugs were known to be completely non-toxic, it wouldn't be a problem. But the potential toxicities could not have been known then, and of course since then problems have come up; lipodystrophy, diabetes, etc.
So the drugs are quite potent. And the one thing an experienced doctor would think about, I believe, in deciding whether or not to intervene in a patient is the rate of progress of the disease in that particular patient. One of the striking things about HIV is the huge variation in the rates of disease progression. But what those guidelines did was to ask one to make a decision based on a snapshot. Well, we know about blips in viral load; fluctuations in CD4 counts; we know about all sorts of things that say a snapshot does not provide enough information.
The fact is there are no emergencies in HIV medicine -- with the exception of people with very low T-cells, of course. But if you're dealing with anybody above 200, there's no emergency; it's not life and death, and you can wait a little while to get a fuller picture. So I think what may have been important in my practice was that I didn't follow the guidelines as they were written when they first came out. As it turns out, more recent revisions of the guidelines seem to be a little bit more in accord with what I actually did.
BH: What would you do?
JS: I would suggest starting treatment at a time when there was a consistent increase in viral load over maybe six or nine months; a decline in CD4 cells; or development of symptoms, whether it be thrush or some other. So it was individualized, and I think it is very important to individualize treatment to the rate of progress. In effect that translates into not starting early. I would start patients where there were stable signs of progression. There were other cases where people were worried and wanted to start treatment and of course I didn't withhold it.
BH: If you saw a change in the rate of progress would you start sampling that person's viral load and CD4 count more frequently?
JS: Yes, I would.
BH: In New York City, nearly 30% of people with an HIV diagnosis also receive an AIDS diagnosis within one month and I imagine many of these patients present as emergencies. It seems your practice was not exactly a cross-section of all the patients who are out there in New York today.
JS: No, as I said, most of the patients I'd been seeing had followed me from my private practice to the clinics at Cabrini and St. Luke's. But that doesn't mean I didn't have experience with the clinic patients as well, and if I had more of them I might have a different story to tell. But on the other hand there are some things I did that were different from what many other people do.
The second thing that I didn't do was switch drugs at the drop of a hat. And I have a sense that that may be quite important. I tended to keep people on the same treatment even if they had detectable viral loads -- as long as there was not a consistent increase in the viral loads. As a result, a good number of patients in my practice did have detectable viral loads while on treatment but they didn't increase and they did just fine. Not everybody; some of them did start to increase and that's another matter.
This, again, was against the dogma. You open a manual of HIV medicine education for physicians and you will see: "What are the goals of antiretroviral therapy?" Well, "the goal of antiretroviral therapy is to produce an undetectable viral load using the most sensitive assay available." And that's based on all the theories of viral evolution. But we assume too much and we don't know the whole complexity of this: we don't know about mutations that compensate; mutations that resensitize.
I should also say, as far as viral load goes, on principle I never used the under-50 assay. I wouldn't do it unless people asked for it. I didn't use it because what am I going to do if it is 200 or 300? I'm not going to do anything.
BH: Let's say you saw two in a row at 1,000 copies.
BH: Okay, one's at 1,000 and the next one is at 5,000.
JS: I'd wait a little bit more. It kind of depends on what the CD4 count is and what the clinical stage is, too. There are people who will tolerate 100,000, actually.
BH: Well, doesn't the probability of developing resistance mutations go up as the rate of replication goes up?
JS: Well, that's true, but you have to rely on empirical stuff, too. And what we ought to do is recognize that there are people around with detectable viral loads of 20,000-30,000 on treatment ever since these drugs became available and they are not going up. Now, what is it? They are full of mutations. We could learn something from these people and recognize that the phenomenon exists. It's easy to go along with the Darwinian thing and selection and escape, and of course I believe all of that, but there are complexities in there that are not taken into account. We don't know enough about mutations that may compensate; that may have an effect on fitness; that may resensitize the virus to other drugs. It's something that you have to learn from real life, and we do have these patients with detectable viral loads and they're full of TAMS and they're with us and doing just fine. I've had patients with a viral load continue on treatment and it hasn't gone up, but everybody is different. I think every patient will contribute some degree of viral control themselves; it's variable; it's more or less; so you have to tailor things to each person.
I've said there is a gulf between academic doctors working from the book, who only see patients in the clinic once or twice a week and don't deal with patients at the end of the telephone because they've got residents to do that. They're not field doctors. On the other hand there are on-the-ground doctors who have observations. I've been told it's just a question of time and don't be silly. I've been at meetings when I said I had patients with viral loads who've been stable for years and I've been told I was lying.
So I can say that part of it is because I didn't change regimens quickly. I know others will change on a single viral load increase before seeing if it was a blip or if it was sustained. Their idea is to keep people 100% undetectable, and I think that has hurt people. That is my own belief. Of course there are instances when you have to change. But where do doctors get their information? They are instructed by academic doctors and this is common dogma: you've got to get undetectable, and you've got to stay undetectable, and if the viral load creeps up...do something. This was more in the earlier days. I think people are much more tolerant about this now because they've seen what the effect was.
BH: Did you use resistance assays?
JS: I did use them. Not all that much, but there were times when they were important, for example with the NNRTIs -- if you get a K103N, that's bad news.
Another thing I know I did differently is that I had a predilection for using nevirapine (I didn't care for Sustiva because of its neurologic side effects, which I think are much worse that they tell us.) At that time I was doing clinical research at CRI (Community Research Initiative), and I was the principal investigator for trials for nevirapine and delavirdine, so I became familiar with NNRTIs and nevirapine in particular, so I stuck with what I knew. I have had a few rashes, but it wasn't so terrible; and I have had a few liver problems, but it was alright; we just stopped and that was that. But by and large I had a good experience with nevirapine. So in those days in 1996, I did things differently, because I tended to start people on an NNRTI, rather than a protease inhibitor.
I went to one of these company marketing meetings once at the Waldorf Astoria where they give you a little box and everyone in the audience votes their choices to various clinical dilemmas. Press "A" if you'd do this, etc. They'd present you with a patient and give you five options and ask what you'd start them with. One choice was an NNRTI and two nukes, so I pressed that button, and when they showed the results I think 2% chose what I chose and everybody else was choosing Crixivan and whatever else. And the moderator said, "I wonder who those one or two people are?" And I felt like ducking under the desk. About five years later I went to another meeting and the same question was asked and this time about 60% of them chose an NNRTI and two nukes. Now, nevirapine is an unforgiving kind of drug because you can lose the whole class if adherence isn't good, so that brings in another aspect of what I did differently.
I really think an essential ingredient for success is the relationship between the doctor and the patient. I have come to the view that in HIV medicine more than any other field, the nature of the doctor-patient relationship is absolutely key, particularly with people who are on treatment. When adherence became a big issue, a lot of money was available, and people were hired as adherence counselors, and it was all for the patients. It was all crap. They should have had counseling for the doctors. Maybe you wouldn't call it adherence counseling, but I'm not joking. In order to be an HIV physician there are certain attributes you should have or you should think about doing something else! It's labor intensive and if you choose this profession you ought to be willing to give up a bit of doctor sanctity, if you will, and make yourself available to your patients to a greater extent than in other fields. That's awfully important. You're actually endangering people if you don't have these qualities.
How you present the ARV regimen and how you choose it together with the patient is very important. Don't present it in a threatening way. I've heard of doctors who said, "If you don't do this you're going to die." If you hear something like that and you aren't taking your pills regularly, you're not going to tell your doctor. What you really want to do is let the patient feel that you are working together as a team -- as best you can; you can't always achieve this, and maybe not even that often, but do as best as you can. And don't make the disease sound trivial either; it's not a chronic manageable anything. Tell your patient that there is work involved, and that their life is never going to be the same again but we're going to try to make it okay. But let's not kid ourselves that this is a walk in the park, you know. Despite all those ads, you're not going to turn into a mountain climber.
BH: So you tried to make them feel like it was a mutual journey.
JS: What I really tried to do was make it possible for patients to tell me if they were having any trouble with the medicines. Everybody is different as far as side effects go: some people will swallow Norvir like water; there are other people who just sniff it and can't stand it. Some people get Viracept diarrhea which is horrible; and others just get a little. Some people can take a million pills without thinking about it and they stick to it; and others can't deal with it. So when it comes to the number of pills or the side effects profile, it's good to work out with the patient what they can live with. So you just have to try the regimen. If they have a reaction with diarrhea or nausea, then you try to keep away from what is causing that. But the most important thing is they have no hesitation in telling you what their situation is. How many patients don't tell their doctors the truth? It's a lot.
The objective is you want to be able to relate to the patient in such a way that if that patient has a problem -- say, nausea -- that you may not think is terrible (but it doesn't matter what you think) then one should be in the kind of relationship with that person that they can call you and actually get through to you -- not an office person or not get a return call or something. That's not for HIV medicine. That may be okay for other things, but it's not for HIV.
So you have to get to understand your patient a bit -- unless you have to start treating them because they are really sick with PCP or something -- but the more usual thing is that you get to know them first. And you might find that some people are better left untreated because it's going to be a disaster story if you try to treat them.
You have to get patients to have some sort of trust. I can think of one clinic patient, he was declining and it just seemed awful, and it involved a 15 minute discussion. I remember we made a deal and I said I'm going to put you on some heavy duty stuff -- we've got to get your T-cells back -- but I promise you that within three or four months I'm going to make it easier for you. Now, I don't know about induction/maintenance; it hasn't been sufficiently studied, but in this disease you just have to do it; you can't wait for the studies. So there's every reason to think that this concept of induction/maintenance may be perfectly viable, and as far as this gentleman was concerned, it was the only viable thing because he was not going to stick on the Kaletra and whatever else I gave him forever. And when the time came, he opted to change and I said I think we'll need another month, but after that I did change him to an easier regimen and he did okay. So building up that kind of relationship where you can discuss these things is time consuming, it's a little bit labor intensive, and it may not be entirely practical, given the volume of patients, the reimbursement situation, and the need to see many patients. But it's so important.
BH: So in an initial conversation with a patient, you'd talk about much of what we've been talking about here?
JS: Yes, although it depends. If someone just had PCP as their first diagnosis, I'd have a different conversation. But part of the conversation with a person who is feeling well, is telling them there is no urgency; there are really no emergencies in HIV medicine -- with some obvious exceptions. But otherwise there are no emergencies, so you can afford to look and see what is happening. So I would ask people to let me observe them. I would say that everybody progresses at a different rate. I would say, maybe you're a fast progressor; maybe you're a slow progressor. I have no idea, but we'll find out. And mostly they've been comfortable with that. Sometimes they were anxious and wanted to be on treatment. And other people didn't want to be on treatment; they hated the idea, so they were quite willing to go along with this kind of thing. But when they finally did go on treatment, they knew that they had to. So when the time comes and it looks like things are going wrong the whole compliance issue is a little better.
So, just to go back again, I don't know why I've had the success I've had -- and I'm not bragging or boasting -- but I do know that I've had a very loyal group of patients. Also I think part of it is that I have had some disregard for official recommendations. I'm not suggesting that people do that, but I had been an academic physician, I was in the virus lab for 15 years, an associate professor for eight years, I had a very traditional infectious diseases upbringing, including in immunocompromised hosts in the transplant field before HIV. So I think I'm capable of making some judgments and I'm not saying one should in principle not listen to authorities -- that's not the point I'm making. But in my particular case, I haven't respected some of the advice that's out there and I haven't followed it, and I think my patients have done better. But that's sort of selective and we need to have some research.
Another thing, and this is just a personal opinion, but I don't think it is reasonable to expect young people to be on these potent drugs for the rest of their lives uninterrupted. Therefore the need to develop strategies of interruption is absolutely critical and I can't see where the opposition comes in because, if you don't accept that, then you accept the principle that a young person is going to be 30 or 40 years (we hope) on drugs, the full toxicity of which is not known. So I don't know what form the treatment interruptions will take, but that seems to me to be such an obvious thing to do.
The other thing that I have done with a few patients is cycling the drugs -- actually it was Mike Mullen who first suggested it and I thought it was a great idea, and I believe there are some studies on it now. The theory is that since the drugs have different toxicities, if you go off a combo that makes you undetectable, you can always come back to it. So if you have a liver-related toxicity, it might be reasonable to give the liver a rest every year or so as a way of toxicity management. Of course, these need to be studied. And when people are used to something, they are very reluctant to change. I've tried, and sometimes I've succeeded, but people are reluctant to change.
The issue of salvage treatment should be discussed in a different way, because it tends to boil down in the discussions to adherence: "You failed because you didn't take your drugs properly." I think that is valid, but it is begging the questions underneath that. That just dumps everything on the patient, but it is the patient, it is the doctor; the economy, the economics of practice; the traditions of practice; it's the communication between patient and doctor; the need to see a certain number of people; clinic structures; managerial interference. We've tended to put it all on the patient and think we can solve the problem by hiring an adherence counselor. And the thing about salvage is that it may be the person who reaches salvage is not going to succeed because there's something about that individual where nothing works.
I've thought we should look at people in the database who'd reached the point of salvage and try and see what it is about them: how many different drugs; what was the trigger for changing; adherence issues? So I think it should be looked into as more than as just a case of a bad patient; a naughty patient who is not taking his drugs.
BH: Did you observe a lot of lipoatrophy or facial wasting in your patients?
JS: Well, yes I did, unfortunately. I tended to shy away from the full dose of AZT more that most, and I'm happy to say that I never have written a ddC prescription in my life. But I did use ddI, d4T, 3TC, because that's what we had at the time, and of course AZT, and abacavir when that came out. So with the d4T, there was lipoatrophy, but I didn't know it at the time; and who did know it? So, sad to say, I've seen a fair amount.
BH: How concentration conscious are you? Do you think about all the factors that can affect drug concentration?
JS: I think that's important. I know there are huge variations in some of the drugs. But I don't think about concentration problems very frequently. Not with the standard dose. I think there is a bit of overkill in the standard doses. I think one tries to aim for a very comfortable level above the minimum inhibitory concentration. You want leeway, and of course people metabolize things differently; and there's not much you can do with the nukes because serum levels don't tell you a whole lot.
BH: Did you use atazanavir unboosted?
JS: No. I wonder if people do? I don't know. I never do. I had one person who wouldn't take it because a friend said, "Oh you're going to turn yellow!" Well, you've got to listen to that. I could have talked him into it, and I can't remember whether I did or I didn't.
BH: Did you have many turn yellow?
JS: I had some, but the same thing happened with Crixivan. But it bothers some and others couldn't care less. So what I take home from this and all my experience, which is coming to an end now, is that, more than any other kind of medicine, HIV medicine involves a closer, more intimate kind of relationship with one's patient, and that may not be attainable given the economics of practice. But if you go into that branch of medicine you should accept that and be willing to try.
The compliance problem underscores the complexity of it all; not these simple-minded solutions, these mems-caps and hiring an adherence counselor and beating on the patients: "Studies have proven that if you're not compliant you will fail!" That leads to a punitive, coercive approach: "You're going to die unless you take your pills!" Instead of saying, "Okay these pills aren't working; you're not taking them. Let's talk about it. We have something else for you. We'll find something for you. Give me a call if it is bothersome."
BH: I wonder if it is practical to conduct a practice this way any longer.
JS: I gave up my private practice because of financial reasons. I was doing clinical research at CRI and I was only seeing patients half time, and with the managed care and the billing, I just couldn't afford to keep it open; it was more than I could deal with. So I went to work in the clinic, but my patients came with me. Most of the clinic patients were originally my private patients. About 70% I'd say came with me. So, again, it may not be me as much as the practice and the patients that had that relationship with me that they would follow me from my practice to Cabrini then to St. Luke's. Not all of them liked it but they did it, so that is a factor.
BH: Have all of your patients found new doctors now that you are retiring?
JS: No, some are still calling me. But they need to find a new doctor. I'm almost 73 and it's no good. I can't tell you how difficult it was trying to match people up with new doctors. And the anger some people felt towards me was very hurtful, actually. Well they trusted me. You spend so much time with a doctor and you have to go through the process of finding someone else...
BH: I imagine a lot of people just won't go to the doctor again for a long time.
JS: Yes, there's one guy who called me a few months ago and asked me for new prescriptions because he hadn't been to see anybody.
I see doctors and I see the barriers they put up. Maybe it is necessary for the economics or maybe for the doctor's emotional protection. But I've certainly gone to visit people in their homes. And maybe it has a kind of ripple effect, because people hear that you do that, they'll know that you'll come. Maybe it adds to the way that people trust you, even though they don't require you to visit, they know that you would do so.
Maybe there are some patients who would feel uncomfortable with somebody who was not gay, but not all gay men. There are women doctors and some gay men feel comfortable with them. It's as if you're in this disease and you have to undergo a kind of obstacle course. It needn't be charitable, but nobody should make the mistake of saying it's going to be alright and you're going to climb mountains.
It's the same thing about safe sex, I believe. If you try to eroticize safe sex you're actually defeating yourself. I think the thing to do is be upfront and honest and people will listen to you. So you say, it's not as good as the real thing, unless you're into rubber, but this is reality. That's it. Life sucks. We can make the best of it, but don't pretend that it's actually a turn-on, because that becomes absurd. And it's the same with this: taking pills everyday; having to go to the doctor; having to know your viral load: it's another way of life. The anxiety you feel every few months waiting for your results; stuff like that affects people in different ways but nobody can pretend it's easy. It's a different life. It's not the same any longer. The idea is to recognize that and be supportive and not exaggerate.
I feel blessed that I don't have to do these things. I have high blood pressure and I have to take pills but they have no side effects and I'm very compliant -- because I know that I ought to be and I see the consequences of high blood pressure -- but the pills don't have any side effects.
If HIV medicines were like that there would be no problem. Just go on them. There's not a downside, other than the cost. That's why I feel that if the answer remains only in drugs, then were going to have to work out some different forms of treatment that involves interruptions, where someone may manage to do nine months out of each year.
This article was provided by Gay Men's Health Crisis. It is a part of the publication GMHC Treatment Issues. Visit GMHC's website to find out more about their activities, publications and services.