The Body Covers: The 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention
IAS 2007 Highlights: An Interview With Pietro Vernazza, M.D.
July 25, 2007
Probably not one single study. It's a group of studies that informed me that we should probably in clinical management make more of an effort to focus on cardiovascular risks that are not really related with HIV: smoking, etc. I think we should have done more in the past in that field, and we realize that the contribution of treatment in that field are very little and treatment itself is so important that we should start earlier in most of our patients. I think that was quite clear here.
One study that I thought was really very important was the PREDICT study because it was the first time that I know of that genetic measurement actually helped us to guide patients in a very significant way. [Click here to read Dr. Daniel Berger's coverage of research on HLA testing presented at IAS 2007.] The PREDICT study will help us to put patients on a very well-tolerated drug.
This is genetic testing for HLA-B*5701?
Exactly, genetic testing for abacavir hypersensitivity. It's probably almost 100 percent [accurate]. If you have done this test you will not see this problem anymore. We will see more of this in the future. At least in our center, we will test all our patients the first day they come in. Together with the resistance test, we will do the abacavir hypersensitivity test. That is probably the single study that impressed me the most.
It's one that will have clinical implications immediately.
Yes. I already set up the system. We start right now.
So as far as the "when to start treatment" debate, have you changed when you start people on HIV treatment? And if is so, why?
Personally, I have been convinced for many years that treatment should have started earlier. The only reason we started later was because of side effects. Now that the side effects have become clearly less and less we must adapt the treatment initiation guidelines.
For many years I have thought that HIV-infected people look like elderly people. Their skin is different. They have cataracts. They have aging signs in their lymphocytes. They have aging signs in many organs. A friend of mine who is an immunologist told me a long time ago, "I think this is immune activation." That is another thing that we realized here, that was discussed here, that it's actually immune activation that's probably driving the aging process. If I can stop the aging process in an HIV-infected individual who is more rapidly aging, gets more cancer, etc., why shouldn't I do it as soon as possible? Immune activation is the driving force of the aging process. [Click here to view or listen to Dr. Brian Gazzard's lecture on HIV and aging at IAS 2007.]
So what CD4 count is the new magic number to trigger initiation of HIV treatment. It used to be 200. Is it now 350? Or do you start patients earlier?
Even now if I have a patient who understands and is convinced [that starting HIV treatment earlier is a good strategy], I start regardless of CD4 count. Personally, this is what I would do. I would take a treatment as soon as I can and take it as long as it didn't cause any side effects. So if the treatment is well tolerated, I would take it. [Click here to listen to Dr. Joel Gallant's discussion of research presented at IAS 2007 on first-line therapy and starting HIV treatment.]
Even immediately after being diagnosed with HIV?
Right. Exactly. And that is also coming to primary HIV infection. That is also what we do in primary HIV infection, because we have this hope that if we start [antiretroviral therapy] very early, after seven or ten years we might have the chance that even the latent [HIV] reservoir will be depleted.
But do you catch a lot of people during acute infection?
It's still a theoretical approach.
We catch a few, one in half a year, or so. But it's not the majority.
Do the treatment guidelines in Switzerland still say treat before the CD4 count falls to 200, or have they changed?
No, we haven't been very vigorous in the guidelines. They are more or less open. The most important part of the guidelines is that you start when the patient is ready for treatment, and I think that is still true.
So it's focused on adherence?
What do you think was the most important advance in our understanding of HIV treatment and care in the last year or so?
I think we started to learn that almost all protease inhibitors, almost all non-nukes [non-nucleoside reverse transcriptase inhibitors or NNRTIs] have metabolic consequences. It's clear that boosting a protease inhibitors will increase it's effectiveness, but also [increase] these metabolic side effects. I think we have to learn to reduce these side effects, but also to live with them, because the advantages just outweigh the risk of the side effects.
Do you think we are any closer to understanding cardiovascular complications in people with HIV? Is it HAART? Is it HIV?
I think what we heard here, and also what SMART [the Strategies for Management of Anti-Retroviral Therapies study] showed us, is that immune activation is probably the driving force for vascular disease. It also is related to the observation that statins -- even with normal lipid levels -- actually reduce the risk. Statins also reduce immune activation. So this fits quite well together. Personally, I believe that this is the mechanism that drives the arthrosclerosis and the cardiovascular risk.
So do you use statins in your practice?
Yes, we do.
Even as a preventive measure in people with normal lipid levels?
No. Not yet, but we try to treat the HIV infection, which is probably the most powerful method to reduce immune activation. But you're right, there might be some residual activation that we could further reduce.
I have two more questions. Do you think we are any closer to understanding the metabolic complications of HIV like fat accumulation and fat wasting -- how they occur and what to do about them?
I think we have noted that the nukes [nucleoside analog reverse transcriptase inhibitors, NRTIs] contributed much more than we ever anticipated. We have learned to improve our methods to reduce the exposure to any drug. Also, monotherapy trials that have actually not been shown here are in my view a good way to reduce the exposure. There will be more and more studies on this field.
Finally, do you think that circumcision should be adopted in the developed world for HIV prevention. If not, why not?
I think that if you look at the data, it is very clear that circumcision will reduce the risk of transmission. [Click here to read or listen to an interview on using circumcision to prevent HIV transmission with two epidemiologists for the U.S. Centers for Disease Control and Prevention. Click here to read, view or listen to presentations on circumcision made at IAS 2007.] It's also very clear that it will be difficult to implement such a program. The interesting thing about circumcision is that circumcision is put forward by people, many men from the United States, who are circumcised themselves. It's interesting [to me], as a non-circumcised man. I still believe that the skin that is taken away with circumcision -- it's true that it is a very delicate skin that is at high risk of high risk of getting infected with HIV, [but] at the same time, it's also very sensitive skin. At least in my personal experience, or impression, and also when I talk to other men, they tell me that the foreskin is actually a very sensitive organ and is part of their sexual life. So I'm not sure how simple it is to convince a man to take off that piece of foreskin.
I heard an interesting remark at one of the talks. I don't remember who said it, but he said, "Oh. This is good. Circumcision, that's like a natural condom." I think that's what it is. It also take away the sensation, which an actual condom does. So I thought that was sort of funny, this natural condom issue. I think in the all the discussions and all the debates that I heard, there's never been any discussion of what the differences are in terms of sexual pleasure.
I think that's an American issue. I think Americans don't like to talk about the sexual pleasure. That is probably why there is no [discussion of this] issue, but I think it's an important issue.
Isn't it also true that the reason we want to circumcise men in Africa, for instance, is that transmission is largely heterosexual there? By circumcising the men we are protecting them from getting HIV from women. That kind of transmission is very unusual in the developed world. Is that not true?
That is true. Mechanistically, I understand very well why it would be a very good plan to do circumcision in Africa. The issue is that I think the plan is set up by people who are themselves circumcised. They don't understand the potential hurdles that they can expect from people who still have their foreskin.
I don't know if you saw the news reports, but I think that it was in Swaziland that men were lining up to be circumcised. When people heard circumcision could reduce their risk by 60 percent, they weren't thinking about sexual pleasure. They were thinking about something else, I think. [Click here to read about demand for circumcision in Swaziland.]
I think it's good. If we can convince these people this is the right thing to do, that's great. But I have a little bit of fear that these men also have some concerns about what they are going to lose and that we are not properly addressing that.
It is ironic that the people who are recommending circumcision are probably circumcised.
Especially from a European point of view. It must be kind of funny.
Well thank you Dr. Vernazza!
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