August 26, 2009
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Welcome to TheBody.com's coverage of the 5th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (known as IAS 2009), which was held in July 2009 in Cape Town, South Africa. Although this conference focused mostly on developing world concerns, there was a fair amount of interesting general research.
I always like to get the activists' take on the research and so I was pleased when two well-known U.S. HIV/AIDS activists agreed to do an interview. Robert Munk, Ph.D., became involved in HIV/AIDS activism in 1987, the year he tested positive. Since then, he has worked in different positions in the HIV community. In 1997, he founded and continues to coordinate the AIDS InfoNet, a patient education resource. He also participates on numerous advisory boards and international scientific conference planning committees.
Also with me today is Matt Sharp who, like Bob, has a long history of advocating for people with HIV. He has a 10-year history of writing about HIV/AIDS and was the education director at Test Positive Aware Network in Chicago, Ill., before his current job at Project Inform in San Francisco, Calif., where he is the director of treatment and education. Both Bob and Matt attended IAS 2009 and agreed to discuss some highlights from the meeting.
Bob, you've been going to these conferences for a long time. Are you feeling more optimistic or more pessimistic about the latest HIV research? Do you think that HIV researchers are really answering the critical questions that most people with HIV are dealing with and want to know the answers to?
Bob Munk: I'd have to say that the high point was really the Vancouver International AIDS Conference [in 1996], where there was the exciting introduction of triple therapy and protease inhibitors. It hasn't quite panned out as much as people had hoped, but it was a huge high point and it was the great big ray of hope at the time.
Ever since then, the results -- in terms of the developed world -- have been a lot more incremental. The more recent developments that I think are exciting have to do with the development of the integrase inhibitors, which as a class, I think are very exciting. But there's also more coming out about complications, which obviously are not very exciting.
Matt, what about you?
Matt Sharp: When you hear a presentation or when you read an abstract, it almost always ends with "More research is needed." Though there's been a lot of progress, especially in HIV treatment, as Bob said, in the developed world, there are still a lot of issues with complications.
In general, the conferences provide a lot of good information, but as I've learned over the years, you don't usually get a big breakthrough as in the Vancouver meeting. It's generally very incremental progress.
In Cape Town, it was really fascinating to see the disparity between the North and South, in developed countries versus developing countries and underdeveloped countries. For many people, it was probably really exciting to have a major international conference in Cape Town with the majority of the presentations focused on issues in the developing world, operations research and self-worth.
-- Matt Sharp
Do you think that by holding such an international meeting in South Africa, more people will be moved by the tragedy in South Africa? I think only 30 percent of South Africans who need HIV treatment actually have access to it. How was it being there when you know that to be true?
Matt Sharp: I was incredibly moved by an opening-night march full of African activists. There I was standing in a crowd of African people. I was one white gay man in a crowd of many -- though I'm sure there were other white men there. There was a huge mob of people. It really was motivational. It made me remember the days when we -- here in the States -- were in those same kinds of rallies and demonstrations. But there I was in Africa, this many years later, and people were clamoring, demanding, begging for treatments that we've had for years in the U.S. and in Europe.
Bob Munk: I'm very encouraged by the response of international foundations and donors to the issue of treatment in sub-Saharan Africa and in the developing world. It's a truly phenomenal response from major players like the Bill & Melinda Gates Foundation, the Clinton Foundation and PEPFAR [U.S. President's Emergency Plan for AIDS Relief]. It's unprecedented, I think, globally in terms of fighting a pandemic.
What I think is sometimes problematic is taking the developed-world perspective to the developing world. For example, the DART [Development of AntiRetroviral Therapy in Africa] trial was reported in Cape Town.1 It assessed clinical outcomes when the results of viral loads and CD4 testing were available to the clinicians versus the results of treatment-change decisions that had to be made solely on clinical outcome. It is a large study, with over 3,000 patients. One of the important things it showed is that good clinical research can be done in the developing world. But the outcome of the study was that the clinical results were virtually identical whether or not the results of viral load or CD4 testing were available.
I think that that's an incredibly important finding, because I think researchers from the North would almost consider that study to be unethical. Like, "How could you even think of not providing viral load and CD4 results?"
But the reality on the ground was that the results, in terms of patient outcomes, were not significantly different. For me, that raises a very critical long-term question, which is: If we do shake loose more money for the developing world, do we want to put it into developing CD4 and viral load capabilities or simply in purchasing more antiviral medications so that we can get above that 30 percent figure that was mentioned?
Matt Sharp: What concerns me about that as well is, here in the U.S. where funding is being cut (especially here in California where we just had a major cut by our governor via a line-item veto on therapeutic monitoring), people might try to apply the findings of the DART study to what we have here already.
So you don't think that somebody listening to this in the West can go without his or her CD4 count and viral load monitoring every three months and be OK?
Matt Sharp: No, because that's the standard now here in the West. The study was done in Africa because they don't have the capability to pay for those diagnostic tests and so they needed to determine if they could effectively treat without them. But we in the U.S. and developed world are able to make use of those tests and should therefore continue to use them as part of standard care.
-- Bob Munk
Bob Munk: We cannot simply apply the developed-world model of care to the developing world. It's unaffordable. On the other hand, I think that when it comes to some of the medication choices, we do want to apply those. I think that the continued use of stavudine [d4T, Zerit] in the developing world is borderline criminal.
A lot of readers are unaware that HIV drugs that are no longer used in the West, because they are considered toxic and because we have better options, are used instead in resource-poor countries. There were a bunch of studies presented in Cape Town that showed that people in Africa are now experiencing facial wasting and body wasting because they're on d4T. However, we knew that would happen going in, but we didn't do anything about it because otherwise they would have no access to treatment.
Bob Munk: Exactly.
Matt Sharp: Pedro Cahn gave a really good talk about the different standards and in the middle of his speech he said, "Say no to d4T."2
I'd never heard a doctor or researcher at a conference pick out one specific drug. He was referring to the developing world, but it was really, really good to hear, and he received applause.
The problem is that international funders are providing d4T. It's a complicated patent and price issue. [Read more about this here.]
Matt Sharp: It is.
I think HIV-positive people who live in the South or in poor neighborhoods in the U.S. can relate to their counterparts in the developing world. People with HIV in many rural areas of the U.S. often don't have access to transportation. In some states, a lot of the drugs they need to help them deal with the side effects of HIV or HIV medications are not covered by public insurance. We have big issues here as well.
Bob Munk: Yes, we do and it's important to remember that. At the same time, when you go to a conference in the developing world, you're talking face to face with people who have to walk miles to get to a clinic to get their medications. It's a different order of magnitude. However, you bring up a very, very good point, which is that there are parts of the United States where the rates of infection are similar to those in sub-Saharan Africa. There are parts of the U.S. where access to care is a major issue. We need to be more aware of those and responsive to those disparities.
-- Matt Sharp
I have a list of the most interesting research from IAS 2009 that I want to discuss. Let's start with PrEP. From what I could tell, based on the conference program, it seems as if PrEP is coming of age. And for people who may not know what PrEP stands for, it's pre-exposure prophylaxis, or in plain English, HIV treatment to prevent HIV. It entails taking an antiretroviral pill some time before a possible HIV risk. What do you think about it, Matt?
Matt Sharp: A major focus of my work at Project Inform is PrEP and treatment as prevention, or treatment for prevention. I'm encouraged. It's out the barn door, so to speak, in terms of the research. There are nine clinical trials ongoing or planned right now around the world to see if PrEP is going to be effective.
But there remains a huge amount of concern and information that we do not have yet about how it's going to be rolled out and how it's going to be paid for. I'm on the fence regarding whether it's going to ever be effectively rolled out.
Obviously, the thought of taking a pill to prevent HIV is a very exciting prospect in one way. But there may be negative aspects that haven't yet been discovered. It's just a matter of time, I think, before there'll be some type of PrEP program available, at least in places that can afford to pay for it.
I hear that some savvy doctors are already using it for the HIV-negative partners of positive men. Have you heard that as well in San Francisco?
Matt Sharp: I've heard anecdotes. When you have a sophisticated, privileged population that's able to afford it, there probably are people that are getting PrEP prescribed.
Is the most common PrEP usually Truvada [tenofovir/FTC] or Viread [tenofovir]?
Matt Sharp: Truvada mostly.
And you just take a pill before you take a risk?
Matt Sharp: The studies span everything from taking it on a daily basis, to taking it intermittently, to taking it at the time of exposure, to prior to exposure because the half-life of the medication is long enough that it's assumed it would protect against an exposure.
There are several different ways that they're looking at it. Obviously, the intermittent method would end up being cheaper. We still don't know, but it's being used in different ways.
-- Matt Sharp
Let's discuss the issue of when someone who is newly infected with HIV should start HIV treatment. Do you think that we're getting closer to universal treatment, meaning when someone walks into a clinic, no matter what his or her CD4 count is, treatment should be initiated? Does this conference bring us any closer to this?
Bob Munk: I think that the data simply keep piling up on the side of treat earlier. Though we're going to keep coming back to this issue of cost and what resources are available to provide antiviral treatment. If the resources are there, as I said, I think there's more and more evidence that treating earlier is better.
Matt Sharp: You can't forget that we still don't know what the long-term implications of taking medications for life are. We have limited data. If people start taking drugs earlier in the disease course, what's that going to mean in terms of long-term side effects and adverse events? There's a lot that we still don't know.
There's one trial that has started called the START [Strategic Timing of AntiRetroviral Treatment] study. It's a huge study that will be looking to see if starting treatment at a CD4 count of 500 has a benefit. But it's still five years away and recruitment's going to be a challenge. There's a lot of disagreement in the research community as to whether the resources being spent on this study are something that should have happened or maybe they could have gone to other places.
I saw a webcast of Wafaa El-Sadr discussing immune activation. She talked about something that many researchers have been discussing because of the results of the SMART [Strategies for Management of AntiRetroviral Therapy] study and it is that the early years after someone has been infected may not be as uneventful as we previously thought, that there are processes going on that are really damaging to one's body.3,4 That's the period we've called latency, I believe. Any of you have a way to explain it to people who aren't scientifically very literate?
Bob Munk: I think people still do not understand that. We're used to charting the progress of HIV infection in terms of viral load, in terms of CD4 count and in terms of the development of classic opportunistic infections.
What we're learning, as time goes on, is that there are other things happening in the body, specifically hyper-immune activation. This is when the immune system is on high alert, and it's revving all the time. What we're finding out is that it is not good for that to continue for years. There are inflammatory processes that are part of the way the body fights an infection. Over the years, the negative effects of inflammation add up. As a result, we see higher rates of heart disease, higher rates of bone loss, and higher rates of cancers that are not typically associated or definitive of HIV or AIDS. As time goes on, we're accumulating more and more of this side-effect data. But we still don't really know what's going on during the so-called latency period, except that it's not latent.
Does this only happen to someone who's not being treated?
Bob Munk: No, no. This is going on in people on antiviral treatment as well, because our treatments, again, are aimed at viral load and CD4 counts. We haven't thoroughly studied, and we certainly do not thoroughly understand, these inflammatory processes.
Matt Sharp: We have a limited viral load assay, which counts viral levels to a certain level. What we understand and what we know now is that there's ongoing viral replication that's occurring when latent cells are activated, and so there's an immune system reaction to those viruses.
One thing that I was really excited about in Cape Town was the new and ongoing research trying to unlock the mechanisms for activating the latent T cells so that the virus hiding in those cells can be purged. That is what's considered a functional cure, which is a stretch, but we're not there yet. Obviously, there's a lot of research to do. It's in its early stages. But this whole idea about the latency period and activation of those latent cells is exciting. I was really glad to see that they spent quite a bit of time at Cape Town on those two areas.
Is there a way to monitor inflammation? For example, could one check IL-6 [interleukin-6] levels?
Bob Munk: As Matt said, more study is needed. The SMART study,4 which produced pretty dramatic results, has provided an incredible service to researchers by creating a huge library of samples from the people in that study. The real value of these samples is that we know the clinical outcomes of the people who gave those samples. These are going to be used for a series of biomarker studies, and the first of those are just starting to appear.
People are throwing out things like C-reactive protein [CRP], IL-6 and D-dimer, but the first studies are just starting to come out suggesting which of these have the strongest links to clinical outcome.
I think there's going to be a lot of research coming out over the next several years from INSIGHT [International Network for Strategic Initiatives in Global HIV Trials], which is an international network funded partly by the U.S. government. I'm very excited to see what comes out of that.
But a lot of people don't want to wait to find out whether it works or not. Are you guys getting your IL-6 and D-dimer levels looked at?
Bob Munk: No. Not enough is known at this point. Sure, you can get those tests and lower D-dimer levels are better than higher D-dimer levels. So what? What do you do with that?
Are we going to look for a therapy to lower D-dimer levels or are we going to wait until we understand the inflammatory mechanism and try to affect that?
Look at what happened with T-cell counts. Everybody was all excited about boosting CD4 counts using interleukin-2 [IL-2]. There's no question that you can boost your CD4 counts. But the studies that were just now definitively reported show that the CD4 increases from taking IL-2 are not as functional as the CD4 increases from antiretroviral therapy.5,6
I have a crude analogy, which is that it's like putting ice cubes in your mouth and then taking your temperature, and lo and behold, your temperature's lower. So what? I think people are looking into, for example, the increases in CD4 counts that we're starting to see with some of the integrase inhibitors, and trying to understand if those increases in CD4 counts are linked to better clinical outcomes.
There are an awful lot of people who can't get their CD4 counts to budge and they're desperately looking for something.
Bob Munk: Right, right. That is a major focus. I think as a result of the IL-2 studies, people are going to be a lot more cautious about interpreting an increase in CD4 count. They're going to look for clinical correlates, clinical outcomes, before they say, "Hoorah. We raised the CD4 count by 60 cells." We need to know what that means.
Matt Sharp: [David] Margolis is doing work on a drug class called HDAC [histone deacetylase] inhibitors.7 The studies that he's done so far look at a way to activate latent T cells so that the virus can be produced, and then hopefully the antiviral therapies that are in use will work to kill that virus.
So far, the HDAC inhibitors have not been proven to work, but there are some other drugs that have not been tried yet that may be safer and may be a better way to unlock that virus.
-- Bob Munk
Bob Munk: No, but I think what is ready for primetime is breaking the idea of a protease inhibitor plus two nukes [nucleoside reverse transcriptase inhibitors]. That was kind of like the dogma. I think that's pretty much shattered, partly by the introduction of integrase inhibitors and partly by the results of some of these trials using innovative combinations -- innovative compared to the dogma -- and a lot of them are working quite well.
Matt Sharp: What interested me about the Prezista monotherapy studies was that there were actually two studies presented, and they had similar results. When you see two pretty large studies like this that have similar results, it's impressive.
But when I ask the docs, they say, "Yes, the results were impressive, but I wouldn't do it." [Laughs.] Is anybody going to go on Prezista monotherapy? What's the point of all of these trials if no one wants to do it?
Bob Munk: I think there's always a fear of breaking away from whatever the dogma happens to be. Certainly, from my experience living in San Francisco in the early years of HIV, patients drive a lot of the treatment models. If enough patients say, "Doc, I'm going to do it" or "Guess what, doc? I didn't take my nukes this month, and my viral load is still controlled," I think it's going to happen insidiously.
Matt Sharp: The thing that concerns me about those two studies I was referring to is that they're both open-label studies. We still don't have real good hard data to show that it works. The Kaletra [lopinavir/ritonavir] monotherapy studies were all the buzz for a while. It turned out that they're small studies. There's still not been a larger study to show that that's an effective strategy. I think it's too early to definitively say that it's going to work. But there will be people, like Bob said, that will ask their doctors because they've heard about it, and they'll want to do it.
On to Selzentry [maraviroc, Celsentri]: Poor Selzentry, trying to find a place in the universe. Matt, can you tell me about the latest study looking at using Selzentry in people who were never on HIV treatment before?
Matt Sharp: It was a re-analysis of the 96-week data.10 It had a slightly better outcome than the original analysis. To me, what's a little more exciting is the development of a genotype for CCR5, which may end up replacing the tropism assay, which is extremely expensive and takes about three weeks to turn around. For those people who have CCR5-tropic virus, both the MERIT re-analysis and the new genotype might be exciting news.
Would the genotype be available everywhere? Could you tell us a little bit more about that test?
Matt Sharp: It's already a part of the standard genotype analysis; they just run an extra phenotype called genotype to phenotype.
Those are the common resistance tests?
Matt Sharp: That's right. They have a separate additional analysis on top of it. I'm not a scientist, so I can't go into the details of it, but it looks promising.
We've been trying to figure out ways to encourage companies to look for other ways to find out tropism. They all have their problems. They're all expensive. If there were a genotype test, I think that would open up the door for more use of Selzentry.
Well, that should be very hopeful.
Matt Sharp: Stay tuned, because it's not here yet. We have to wait a little bit longer. But this was the first I've seen of this new genotype.
-- Bob Munk
OK, on to an innovative study known as FOTO [five days on, two days off], which is, Bob, not in the HIV treatment dogma. The idea is to see how patients do if they take treatment only Monday thru Friday, skipping treatment on Saturdays and Sundays.11
Bob Munk: I've heard it referred to as the Provincetown party plan.
It's a cute trial, but will it work in the real world? Is anyone going to try it?
Bob Munk: Yes, I think people are trying it. I think that this is a perfect example of what I was talking about, that patients will try something on their own. As long as there are published results, which there are in this case, that say this could really work, I think people will be doing it.
Could you explain why the particular meds that were used in the FOTO study are critical to the success of this trial? We don't want people on a different regimen to think they can take off for the weekend because of FOTO.
Bob Munk: Right, that is certainly not the case. The drugs used in FOTO, which includes Sustiva [efavirenz, Stocrin], have a very long half-life. They stay in your system for a very long time. In fact, I remember when Sustiva was being developed, some people said that it might have been approvable as an every-other-day drug, but then that would have been a nightmare because who's going to remember which day they take it and which day they don't. However, that means that if you don't take it for a day, there's probably still enough in your system to fight HIV. This is a fairly small study, but the results have been fairly consistently positive.
Matt Sharp: I think this trial is hopeful for people who are tired of taking pills. It's not a treatment interruption study per se because you still have the blood levels in your body. But it's a treatment interruption study in terms of the physical aspects of taking the meds, so that's a good thing.
I was encouraged to see it because there's been a quash on doing any more treatment interruption studies. If the trial is designed right, and if it's the right medication that stays in the bloodstream longer, then I think that these kinds of studies are possible. Who knows what will happen after we get more information in larger studies?
Bob Munk: I see the FOTO study as part of a larger trend, which includes studies on monotherapy and induction maintenance where you would start with a standard regimen and then back off. But now, there are more options being looked at, and I think we have to with people living longer.
If people are going to take medications for 15, 20, 25 years, it makes a big difference whether they have to take pills twice a day or once a day, etcetera. So I'm really glad to see it all.
Is there more to the FOTO study than just the convenience of taking the weekend off? Is it also preserving your body to take meds for 10, 15, 25 years?
Bob Munk: I think it's really foolhardy to make that assumption after the SMART study. The basic premise of the SMART study was that if we take people off of meds when their CD4 counts climb, they will have fewer side effects versus if they took antiretrovirals continuously.
The study very definitively said, "That's not the case." Viral loads increased and the patients had more problems, not less. Of course, that was because people in the SMART study went off of their medications for sometimes weeks or months. But I still think it would be a mistake to extrapolate to the FOTO study and say, "Oh, you're taking less drugs, you'll have less side effects."
There was very little at the conference about cancer and HIV. Is there any new understanding about why people are getting head, neck or anal cancers?
Matt Sharp: Brian Gazzard gave a talk about some of the possible mechanisms around cancers that are caused by viruses that may be implicated in people who are aging, and specifically we're talking about papillomavirus, the cause of some of the head, neck and throat cancers.12 Those cancers are on the increase and that may be because of the immune response in older people, but it may also be because of ongoing HPV [human papillomavirus].
At IAS, there was a study that showed that vitamin D deficiency was more likely if you were taking Sustiva, which was unknown before.13
Bob Munk: Yes. I think that this is an interesting avenue of research because it's so simple to remedy vitamin D deficiency. To look at HIV patients and say, "Take a good supplement without overdoing it, spend a little time in the sun, and we'll see what happens."
Matt Sharp: And then you go in the sun, Bob, and you get skin cancer. [Laughs.]
Bob Munk: [Laughs.]
Matt Sharp: It's an endless circle.
Bob Munk: Yes, it is.
-- Bob Munk
Matt Sharp: I want to talk about diet and nutrition and smoking. If people would really focus on improving their diet and stop smoking, I think that may have a big impact with respect to aging and HIV.
And not worry so much about all this data about aging and HIV. [Laughs.]
Matt Sharp: There's still a lot to understand about how the effects of HIV are strongly related to the effects of aging. Also, there may not be much that we can do about it. I'm thinking that concentrating on holistic health and things like stopping smoking and eating better will have an impact on overall health as they do in people who are not positive.
Bob Munk: It really would. Unfortunately, we've grown up in an era where we look for the magic bullet. We've gotten magic bullets to control viral load and to increase CD4 counts. There is no magic bullet for stopping smoking. Yet, it shows up again and again and again as a major health risk factor. So to be able to address that issue, to be able to address physical exercise, to be able to address diet and lifestyle issues, would probably have more impact than waiting for five or 10 years until some of this research bears fruit, and then maybe adding another pharmaceutical product to your regimen.
Don't you think that not enough physicians are telling their patients that it's a holistic thing, that it's not just HIV, and that they have to take care of themselves and exercise?
Bob Munk: I think that's gaining traction among physicians, but what will that accomplish? Like Matt said, people have been trying to stop smoking for decades. And to use the scare tactic of "Well, it's going to increase your risk of a heart attack," and "It's going to increase your risk of bone fractures," how far does that go? Not very. It's very frustrating.
Matt Sharp: In the [San Francisco] Bay Area, a lot of the doctors have been around a long time, they have aging populations of patients, and they are more interested in a holistic approach.
Is that happening in AIDS organizations as well? Are they doing wellness workshops?
Matt Sharp: Yes. Here in the Bay Area you see more of it. I think in the urban centers, you probably see more of it.
This has been great. Thank you so much for talking with me and giving your take on IAS 2009.
This transcript has been lightly edited for clarity.
No comments have been made.
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