The Body Covers: The 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention
IAS 2007 Highlights: An Interview With Anthony Mills, M.D.
July 25, 2007
Which studies at IAS will have the most impact in terms of changing clinical practice?
I think that we have access right now, through expanded access programs, to several novel agents. So those are really available to HIV practitioners across the country. What we saw in this meeting was some really great data, talking about the efficacy of those novel agents: raltegravir (MK-0518),1,2 etravirine (TMC125),3 vicriviroc,4 which is in trials now but not in expanded access. That data is really important as far as changing the way that we actually practice. It's going to make people feel a lot more comfortable using some of these novel agents, and will certainly translate, I think, into better patient care.
In terms of the "when to start treatment" debate: Have you changed when you start people on therapy? And if so, why?
Yes, I have changed. One of the things that I was most excited about in coming to this meeting was: I wanted to see what other people were thinking and see if other people were feeling the same way that I was. I went to every one of those sessions on when to treat, because, again, it's something that is so important to all of us.
My sense is that the pendulum is really shifting. I was certainly a person who adopted [the notion] pretty early on [that we need to]: Get people off of therapy if it's toxic, if they've got good T-cell counts; wait till the last minute to start their antiretrovirals.
But we have increasing evidence [now] to show that starting people earlier on therapy is extremely beneficial; that the earlier we start, the better people do, the easier it is to suppress the virus, the fewer side effects that they have.
This is also extremely important, as far as HIV prevention goes. My sense in being involved in the field for the last 20 years is that it's been very difficult for us to get on the other side of the increasing scope of the epidemic. My hope is that, maybe, treating people earlier -- getting people on therapy now that we have much safer and better tolerated medications -- will actually help us get on the other side of the growth of the epidemic, as well.
So, treatment as HIV prevention.
I have another question that wasn't really addressed at this conference. Are we any closer to HIV eradication?
That's really hard to say. You're right. I don't think anybody even mentioned the word "eradication" at the conference. I think that, certainly, we're having revealed to us more and more potent agents. Some of the integrase inhibitors,5 for example, which seem to pull the viral load down more quickly, even, than the most powerful agents that we had before; I think that's very exciting. Some of the novel compounds that work in different ways, some of the gene therapy studies that are going on -- those are probably going to be the keys to viral eradication and certainly, hopefully, we'll get there one day.
But we're not any closer yet.
I don't see it on the horizon right now.
What are the biggest open questions in HIV research, do you think?
Right now it's a very exciting time because I think that the treatment paradigm for how we're going to treat the whole spectrum of HIV patients is really going to change. I think that, with the advent of these new agents, new ways of fighting the virus, agents that are extremely well tolerated and very difficult for the virus to develop resistance to -- we're going to see changes in the way that we approach therapy, from treatment-naïve patients to early-treatment-experienced patients who have failed one or two regimens, to our most advanced salvage patients.
That's the most exciting thing for me right now. There is some really wonderful stuff out there. The next few years will help us to sort out how we're going to combine those things and what's going to be the best thing to do for our patients.
Are we any closer to understanding how metabolic complications of HIV occur, and what intervention we should take?
I wouldn't say that we're any closer to understanding why they occur. From the very beginning, there's been this sort of umbrella of lipodystrophy or metabolic complications. And everything that we just couldn't explain, we just lumped under the umbrella of "complications." We still don't really understand why certain drugs seem to manifest some metabolic side effects, and other drugs manifest others. I think we are getting better and better in the drug development process, at recognizing those things early on, and knowing that those aren't acceptable side effects for our patients anymore. The drugs that we see coming to market now are much better tolerated -- as far as metabolic side effects -- certainly in the short term. We're hoping in the long term, because of the increased realization of really how important those things are.
I know you were the lead investigator on the DUET-13 study. Was there a metabolic sub-study or analysis of those?
We looked very closely at lipids and insulin resistance and those things, and patients did extremely well in this study. A lot of patients actually came in with significant hyperlipidemia, because of being on very complex protease-containing regimens that tended to really affect their triglycerides and lipids. We saw those patients improve dramatically over the course of the study. We're really excited about new agents and new combinations of agents, and the fact that they are going to be much better tolerated as far as metabolic side effects go.
Are we any closer in understanding how cardiovascular complications are caused in people with HIV?
I think the SMART study really opened up another whole realm for us as far as: Wow, what's going on here? Because for so many years, we really thought it was a side effect of the medications. Then when the SMART study came out and we started seeing the data there, and the DSMB [Data Safety Monitoring Board] stopped the study. It was because of these terrible cardiovascular complications6 -- not in the treatment group, but in the group that was getting the treatment interruptions.
That's kind of moved us back to this place where we think the cardiovascular complications may actually be related more to this chronic inflammatory process that takes place in the bodies of those who are constantly fighting HIV through the course of their life. Again, this might help us to decide which way the pendulum should swing. We maybe should be treating people earlier, minimize those long-term inflammatory complications, and hopefully diminish the long-term incidence of cardiovascular complications.
Do you think that circumcision should be adopted in the developed world for HIV prevention?
No. I think it's fascinating: there were probably as many talks here on circumcision, and the discussion of this, as there were on when to start treatment. It's interesting, because this is an intervention that we have seen in study after study after study7,8 to be efficacious in stemming the spread of HIV. Yet, we have not moved into a large-scale prevention effort by actually implementing that. There was a lot of discussion about that here, and a lot of interest in that. I think it will be very interesting to see, over the next few years, what happens with that.
Certainly, there are cultural norms and things like that which must be addressed whenever we're talking about recommending something like this to a large population of people. But one of the things that we found in some of the preliminary studies is that populations that we thought were not going to be really receptive actually are pretty receptive. If you can go into a population and offer them an intervention like this, it's going to decrease the likelihood over their lifetime that they are going to contract HIV. If you're talking about a high-prevalence area like sub-Saharan Africa then, absolutely, people should be very interested in that. And I think they will be.
But you don't think it will play very well in the United States?
I think it's interesting, because I reviewed some of this stuff before I came to the meeting. I actually thought, "Do I ever sit and talk with my patients about whether or not they should be circumcised to decrease the likelihood that they are going to contract HIV?" And I really don't. I haven't moved into that. But I think the talks, or the meetings, and the discussion here certainly have moved me to a point where I think that is something I should bring up with my patients. It will be interesting to see whether that's something that's more broadly adopted.
Was gay sex acknowledged or addressed at all in any of the sessions on circumcision? Or were they all focused on heterosexual sex?
Well, that's one of the questions, really: whether circumcision makes a significant difference for the MSM [men who have sex with men] population, or whether it's really just efficacious for heterosexual contact. We don't really know that.
We still have 10%, 15% of our new infections, that the only risk factor they identify is unprotected oral sex. So I think there's still HIV transmission that takes place that we don't really know about. I still have patients in my practice who convert to being HIV positive, who insist that they have never been engaged in receptive anal intercourse, that they only engage in insertive intercourse. Yet, they still convert and become seropositive. So I think that there probably is a role for any of those prevention interventions in the MSM community, as well.
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