This Month in HIV: State-of-the-Art: HIV/AIDS Medications for the Treatment Experienced
Now, I'm pleased to welcome to This Month in HIV Jeff Berry, director of publications and editor of Positively Aware at Test Positive Aware Network, the oldest peer-led HIV service provider in Chicago. He has been working at Test Positive Aware Network in various positions since 1992.
I thought he'd be interesting to talk to since he just finished being immersed in this issue. The March/April issue of his publication Positively Aware is called "Hope for Survival -- Salvage Therapy Revisited." The issue focuses on how HIV therapy for the treatment experienced has changed. On a more personal note, Jeff is also familiar with this subject since he is moderately treatment experienced himself. He has been HIV positive since 1989 and has taken an assortment of HIV medications.
Welcome, Jeff, to This Month in HIV. I'm so glad you could join us for today's podcast.
Thank you, Bonnie. Thanks for having me.
One of my first questions is about the terminology. There are so many terms for someone who is treatment experienced. What does it mean to you, a treatment-experienced person?
One of the reasons, I think, we did this issue of Positively Aware on salvage therapy, is because there is some confusion out there about the different terms. You hear so many different terms. You hear "salvage" and you hear "rescue" and you hear "treatment-experienced," and you hear them used interchangeably. I thought it would be interesting to talk about some people's different experiences in salvage and rescue therapy. But treatment experience to me really just means that you have actually been on treatment. [Click here to browse a PDF of Positively Aware.]
It doesn't mean you're very treatment experienced. It just means that you have had some experience.
Correct. There are actually different levels of treatment experience. You know, we can get into that a little bit. But someone could be moderately treatment experienced. They could be in an intermediate stage or an advanced stage. Just as in HIV disease, there are different stages, different levels of disease, there are also different levels of treatment experience.
I guess when people say, "We need new drugs for the treatment experienced," I guess what they mean is for people who have multidrug resistance.
Right. So your probabilities for success with the different therapies that are currently available are less when you have multidrug resistant virus. If you are resistant to many drugs in one class, such as the non-nuke [NNRTI] class -- Sustiva [efavirenz, Stocrin] and Viramune [nevirapine] fall in that category -- then you are resistant to all [the drugs] in that class; you knock out the entire class. It's much harder to respond to treatment once you have knocked out one or two classes of drugs because you don't have many options left.
What percent of the patients, of people with HIV, are multidrug resistant? Do you know if there's a number?
I don't know that offhand; I'm sorry, I don't.
It's a small percentage, though, at this point.
I think it's 10 or 15 percent. But it's a small number. You have to also keep in mind that HIV resistant virus can be transmitted. Multidrug-resistant virus can be transmitted. This means that if you have never been on treatment and you contract the virus, become HIV positive, you can become infected with a virus that is already resistant to one or more classes of drugs. That's a reason to be even more extra careful in protecting yourself.
I think the number was 9 to 15 percent of patients in the United States with HIV, when they are told they have HIV, actually also have drug resistance as well. These people then start off their lives with HIV already resistant to one or more medications. In the U.S. people who are treatment na?ve and already have HIV drug resistance generally have resistance to NNRTIs, like Sustiva, which is kind of a problem because the only once-a-day, one pill dual-class combination drug: Atripla contains Sustiva. And if you're resistant to it, you can't take it.
Right. It's one of those medications that's on the preferred list for the treatment guidelines, so it's a very powerful drug. It's one that's very frequently used and recommended for first-line treatment.
Going back to terminology -- Which word fits your situation? Do you see yourself as a rescue patient? A salvage patient? A multidrug resistant patient? Or are you just treatment experienced?
You know, I probably fall somewhere in the intermediate level of treatment experience. I've been on many different regimens. However, I have a lot of options still available to me. My immune system is relatively intact. I would be really considered not to be on salvage therapy for those reasons.
If I were to develop resistance to drugs that I'm currently on, then I might be giving you a different answer because of my current regimen. I'm only on two different medications, from two different classes of drugs, and if I were to develop resistance to those then I could knock out two classes, potentially, very quickly. But right now, I'm just treatment experienced, and I'm probably at the intermediate level of treatment experience. I've been on HIV treatments since 1989, but I have been very lucky and very successful with my treatment.
Could you go through a little bit of your history?
In '89, you were on AZT [Retrovir]?
Right. I started AZT monotherapy in 1989, and that was really the only drug that was around at the time. I saw a steady decline in my T cells over the next five years or so. Then I switched to d4T [Zerit, stavudine] monotherapy.
By monotherapy you mean just one drug?
Just one drug. I switched off the AZT and onto d4T.
Was there a reason?
At that point, my T cells had dropped below 200 and my doctor was concerned that the drug was not effective -- AZT -- so he switched me to Zerit, which was a newer drug at the time. And then, not even a year later, I added Epivir, or 3TC [lamivudine], to my d4T. Then about a year and a half after that, in September of '96, I switched to 3TC plus AZT, or Epivir plus Retrovir, which is Combivir -- now known as Combivir -- in one pill. But at that time it was two. Plus Viramune, which was the first time I was on an NNRTI.
But only a few months after that, my viral load steadily increased. That was the first time I had gotten a viral load test, was when I switched to adding the Viramune. It was 20,000, and then a couple months later, it was up to 40,000. They took me off the Viramune, kept me on the 3TC and AZT, and added Crixivan [indinavir]. I did pretty well on that for a couple of years, and went to undetectable. But then I developed kidney stones.
A famous Crixivan side effect, right?
Yes, a famous Crixivan side effect. Even though it was working well for me, when I got the kidney stones, I had to, unfortunately, go off of it, and that's when I switched to Viracept [nelfinavir]. I never really did that well on Viracept plus Combivir, although I had a low viral load. I think it was, you know, hovering. But it was always detectable. It was always above the level of detection. I never could get it to undetectable at that point, after switching off of Crixivan. And then, when my viral load started to steadily increase, and after I had had a resistance test showing that I was indeed resistant to it, I switched to Kaletra [lopinavir/ritonavir] plus Sustiva. I have had great success with that regimen, and am still undetectable six years later on that regimen.
It's a very unusual regimen.
It is. It is. My doctor felt, I think, it was really important to hit hard and, you know, be aggressive, and he had had success with this regimen with other patients of his. The only caveat, or potential drawback, to the regimen is the potential for high lipids, and increased lipids, which, indeed, I have begun to experience. I'm also taking Lipitor to help control that. I may have to switch off this regimen, just because of the potential for metabolic complications and heart complications, but so far I have been lucky to have a very successful regimen with the Kaletra and Sustiva.
You went from, I guess, a low T cell count of 177 to 800 now?
"I have been very lucky for someone who has technically fallen below that 200 level, to come back up to where I am now."
Right. It's anywhere, like, 700, 800 T cells. The immune system is very hardy, in my case. I have been very lucky for someone who has technically fallen below that 200 level, to come back up to where I am now. My ratio of CD8 to CD4 cells is pretty high. It's interesting, because I think everyone responds differently to therapy, to treatment. What works for one person doesn't necessarily, obviously, work for another person. You have to take each case by case.
I think a lot of people, when they hear that somebody has been through a lot of treatments, they think it's odd that they're not taking a newly approved drug. They think they'll have to come up with something really weird, something that's in clinical trials. But the only thing that's different is that it's an unusual regimen, but the drugs that you're taking are very current. They are what are called by the U.S. treatment guidelines "preferred drugs." That's the thing that is not different.
A lot of people think if you're treatment experienced, you're going to be taking maraviroc or another drug that's in clinical trials. But there are a lot of people who haven't been exposed yet to Kaletra or Sustiva, who have been on treatment for years. They just never took those drugs -- and they could be good drugs for them.
That's the whole idea, too. You want to try to spare as many drugs and classes that you can. I know a lot of people who have been very successful and they are still on nukes [NRTIs] and maybe one non-nuke [NNRTI], like Viramune plus Truvada [tenofovir/FTC]. And they have been on that for years and they are doing very well with it. They have never had to even go on protease inhibitors yet.
It's a great option for many people to be able to take class-sparing type of regimens. This way they can save the protease inhibitor class or some of the newer classes like the integrase inhibitors and the entry inhibitors for down the road, when they may need them.
Are you very worried about taking your regimen on time and being really careful with that because you stand to lose so much if you become resistant to either of them.
"... adherence has just kind of become second nature to me. I think it's something that you learn, that you can teach yourself, and you can use different things to remind you ..."
That's a good point. I'm not worried, simply because I was on Crixivan. At the time it was unboosted, when I took it -- meaning, it wasn't boosted with Norvir [ritonavir], which is now recommended. I mean, the only time you would take Crixivan, if you would even take it, would be boosted with Norvir. But back when it first came out, you didn't. You took it every eight hours, and you took it on an empty stomach. That was the most difficult thing, one of the most difficult things, I have ever had to do.
I learned a lot from that experience, in the sense that I was adherent for over two years. I maybe missed one dose in that time. I never developed a resistance, and it was very, very effective. But it was a very, very tough regimen. It was always drilled into me, from very early by all my doctors, luckily, how important it was to be adherent and to stay on and take the drugs on time and to take the right dosages. I would sometimes wake up in the middle of the night just to take my Crixivan on an empty stomach, if I had to.
That experience really taught me, and now adherence has become second nature to me. So I think it's something that you learn, that you can teach yourself and you can use different things to remind you to be adherent. I don't even really think about it anymore. I always take my Kaletra 12 hours apart: one dose with breakfast and one with dinner. And then I take my Sustiva when I go to bed. So it's just second nature, like brushing my teeth.
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This article was provided by TheBody. It is a part of the publication This Month in HIV.
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