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Gains Made in Quest to Understand HIV: Another House Call with Dr. Charles Farthing

HIV Watch

May 1998

A note from TheBody.com: Since this article was written, the HIV pandemic has changed, as has our understanding of HIV/AIDS and its treatment. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information!

Last spring and summer, Positive Living published a two-part interview of Dr. Charles Farthing, medical director of AIDS Healthcare Foundation. In that conversation, Dr. Farthing, who has been treating HIV patients since 1983, and Lee Klosinski, director of AIDS Project Los Angeles' Education Division, discussed treatment options, opportunistic infections, prophylaxis and other topics. Recently, Dr. Farthing was interviewed again by Klosinski, and assessed the state of HIV treatments in 1998.


Q. How has your mind changed or remained the same over the last year about HIV?

A. I think there has been a bit of a paradigm shift in my mind and it was sort of simmering before the last annual Retrovirus Conference. (The 5th Conference on Retroviruses and Opportunistic Infections was held in February in Chicago.) I am absolutely convinced that we are not doing well enough with antiretroviral therapy because it's become very clear that we have to get down to less than 50 copies. We have to chase this virus completely out of circulation if we are going to have long-term, durable suppression of the disease. That's not surprising, because if there is virus in circulation, there is virus replicating, and if there is virus replicating, then there is virus mutating. But now we have proof of this.

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When you look at the results of several studies of triple therapy they are all show similar results: 80 percent of participants have undetectable viral loads at less than 500 and 60 to 65 percent have undetectable viral at less than 50. Clearly, 60 to 65 percent long-term success is nowhere near good enough. And then we see from researchers from the recent Retrovirus Conference held in Chicago that if you use four drugs and five drugs you get faster suppression and deeper suppression of HIV viremia. Clearly, we could increase the 60-65 percent with undetectable viral loads of less than 50 with more potent cocktails. More potent cocktails either means cocktails with more drugs or it means cocktails with two or three more potent drugs.

The comforting thing from the conference was that more potent drugs are forthcoming. We now have nucleosides and non-nucleosides as potent as our current protease inhibitors, at least in development and available through compassionate use. So I think very rapidly that by using ultrasensitive viral load testing, these new compounds and, for some patients (at least those with initial higher viremia) four or five drug combinations, we will do better. Not that we haven't, of course, done colossally well in the last two years compared with how we were doing before. We have emptied our hospitals and made lots of patients well. But it's clear we have to do better.

Q. What do we make of the report suggesting that a return to viremia does not correlate with a return to clinical problems?

A. I think that's a short-term thing. But it's not surprising, and it's not new news. When you think that AZT monotherapy is a very weak antiretroviral on the spectrum of what we have now, and its durability is only about six months, despite it being weak and short-lived, it's still extended life by two years. So if you use a drug three or four times as powerful as AZT, but it does not render someone undetectable for, say, three years, then obviously you've done the patient colossal benefit despite the fact that you never got them to undetectable. So, I think the message from that is that it is still very worthwhile if you bring viral load down and hold it down somewhat. You are not a complete failure by any means if you do not reach undetectable. You benefit considerably. But that shouldn't deflect us from our ultimate goal of getting viral load to less than 50 and trying to achieve a truly permanent suppression.

Q. There's a growing debate about funding of medical and social services for people with HIV disease. What is your perspective as a provider on the "drugs, not hugs," controversy? Is that an artificial dichotomy?

A. Drugs are extremely important. It's not really money for drugs, not hugs. Money for drugs is essential; then there is literally less needed for hospital and hospice care. There are simply less patients demanding those services. So clearly, if you've got a lot of money allocated for hospice work than you need to reallocate some of it because you don't need as much as you did.

And where are you going to reallocate it? Well, drugs is a good place. I don't see a lessening of the support for service organizations, but a different function. It's more like a rearrangement of their budget. Instead of putting a lot of money into food banks, grief counselors or hospice or in-home counselors -- which they must have had a lot of -- agencies should channel more resources into treatment advocates and compliance buddies. They can do a huge amount of beneficial work in that area. Many individuals distrust the medical profession. But if they hear the same information coming from their peers, they may change their mind very often.

So having this liaison between the physician and the treatment advocate or the patient counselor is enormously beneficial. It increases your success rate -- the chance of making patients compliant and having them understand what they need to do, particularly for the fearful and suspicious patients. If you can introduce that patient to a young patient who has done fabulously well on therapy after initially having problems themselves, you can increase the likelihood of that patient understanding the benefit of therapy.

Q. Have your thoughts on eradication changed?

A. Everyone is familiar now with the data from Johns Hopkins showing that there is a percentage of memory T-cells that remain infected as a reservoir that doesn't seem to be depleted at all even after three years of HAART. And in people who have had two or three years of HAART, researchers can deplete CD8 cells, the suppresser cells, and stimulate CD4 cells that are latently infected with the HIV genome and get them to bud virus. If they can do that in the lab then presumably it can happen in the body. So it looks like sterilization (eradication) is not likely.

There are three cases from Europe of patients who have been treated with ddI and Hydrea [hydroxyurea] for nine months to a year and therapy is stopped and there is no relapse in viremia. There was an abstract at the last Retrovirus Conference which suggested that these patients didn't have HIV DNA and virus couldn't be grown out of them using the techniques just mentioned. Well, I understand that those same patients' cells have now been looked at by another researcher who has been able to bud virus from them. So none of these ddI plus Hydrea patients, to the best of my knowledge, are sterilized. However, they are running along without therapy and no viremia. So they have the perfect profile of the long-term nonprogressor. Since they were treated at seroconversion, or close to it, we don't know that they wouldn't have wound up with that set point even without the help of any drugs, because some patients do. However, I suppose that there is the probability that the drugs had some effect there.

This makes me think of another presentation in Chicago by Dr. Bruce Walker discussing the treatment of seroconverters with antiretroviral therapy and what's happening. He looked at six seroconverters and found that if you treat at seroconversion, you preserve both helper and cytotoxic (killer) T-cell function against HIV. Cytotoxic T-cell activity depends on helper T-cells functioning properly. That is exactly the profile of the 3 percent of participants in the San Francisco City Cohort who are long-term nonprogressors after 17 years of infection. So the message from Bruce Walker would appear to be that if you treat immediately after seroconversion you can convert people into long-term nonprogressors. So maybe that's what's happening in these cases. Perhaps, we certainly don't know, you could start therapy with recent seroconverters and they could have the profile of the long-term nonprogressor with no viremia, but that doesn't mean that they are sterilized. It does mean that they are actively suppressing the disease adequately by themselves without drugs using the best antiviral which is the immune system.

You have to realize that many of the viral infections we have in life are not cured. All of us who have had chicken pox still have live chicken pox virus in us, but we are not ill from chicken pox. But if I wanted to grow chicken pox virus out of you, I could probably do it. So it doesn't matter if you can grow HIV out of an individual if their immune system is keeping the disease completely suppressed. However, there are a lot of unknown questions here.

Dr. Marty Markowitz (Aaron Diamond AIDS Institute) pointed to one patient that he had on a triple cocktail who was completely suppressed and who stopped his therapy and remained completely suppressed for four months and then got a return of viremia. So stopping drugs would always be a concern. Even if you stopped drugs and there was no viremia, you would still want to constantly monitor these patients to make sure the viremia didn't return later. And I guess in the future experiments will be done with treated seroconverters who are still positive for proviral DNA. Their drugs will be stopped to determine if viremia remains controlled by the immune system alone.

But I would not encourage patients to do it by themselves. I would encourage patients to find a cocktail that caused them no side-effects and that they could easily adhere to and just stay on it like a hypertensive or a diabetic would. Hopefully, it will keep them well until they die of natural causes sometime much, much later.

Q. What do you think about the development of alternative drug delivery systems? I've heard the molecules are too big for a transdermal patch. What about implants? Are people working in these areas?

A. I've heard a little bit about that. I know some people are working on it. Some people have looked at subcutaneous pumps and some people are talking about subdermal implants. And I suppose that's very important to do research in, especially as we are getting more potent drugs that require less volume like some of these once-a-day drugs like efavirenz and ABT378 and things like that. So ultimately that may be an extremely useful tool for the non-compliant patient if you can keep a constant blood level in them by some sort of device that doesn't require them to swallow a pill. And then, of course, there is the option of the slow-release pills, which is again a type of alternative delivery system, which may have to only be dosed a few times a week and then you could use directly observed therapy to keep the non-compliant patient compliant. We must explore all of those avenues but at the moment they're not very far ahead. So for practical purposes, this year we have concentrated on getting patients compliant with the regimens we currently have.

Q. Can you tell us a little about the current status of a clinical trial using a live attenuated vaccine?

A. The working group I am part of has received a letter from the Food and Drug Administration that says we have approval to go ahead and develop the live attenuated strain in an immortalized T-cell line for human trial. That had been a big blocking point: the fact that it was being developed in a tumor cell line. They were saying it couldn't be used in humans. Apparently they have broken that rule. Dr. Donald Desrosiers at Harvard has developed a more attenuated strain. A good lab practices protocol to insure its purity for a clinical trial is being developed. The trial will be run by Dr. John Sullivan in Boston in terminal cancer patients and then will be followed immediately in physician volunteers. I will be speaking about this and updating people at the International Conference in Geneva. So there has been some progress.


This article has been reprinted at The Body with the permission of AIDS Project Los Angeles (APLA).

A note from TheBody.com: Since this article was written, the HIV pandemic has changed, as has our understanding of HIV/AIDS and its treatment. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information!



  
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This article was provided by AIDS Project Los Angeles. It is a part of the publication Positive Living.
 
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