CROI 2010 Wrap-Up: The Evolution of Antiretroviral Therapy
A Discussion With Joel Gallant, M.D., M.P.H.
March 8, 2010
Joel Gallant: I'm very interested in the whole when-to-start question, and I'm a pretty big advocate of starting people early, even to the point of just starting everybody with HIV on therapy. I think the data at CROI supported that concept, for the most part.
We saw a number of studies that looked at the issue of the CD4 count, including the nadir CD4 -- the lowest that you've had -- and correlating it with the development of certain complications. So, for example, from the large CHARTER study, which was looking at neurologic complications of HIV, they found that your neuropsychological performance on specialized testing was a direct function of the lowest CD4 count that you've had. So if you started out with a low CD4 count -- even if you're on therapy and doing well now -- you have a poorer neuropsychological performance than if you started with a higher CD4 count. Other, smaller studies had shown that before. But I think that's of critical importance in saying that we really need to not be waiting for people to develop low CD4 counts before starting therapy.
There was a group that looked at arterial stiffness as a proxy for atherosclerosis and, again, found that the nadir CD4 count was associated with arterial stiffness. So that the idea is that if you wait too long [before starting treatment], you begin to develop coronary artery disease.
Then we saw that nadir CD4 count was associated with a higher risk of fracture in the HOPS cohort.
So everything just keeps telling me that we need to get away from this emphasis on immunosuppression -- the old idea that, well, as long as you keep your CD4 above 200, you'll be fine. Or you could change that to 350. I think what we're seeing is that HIV does bad things to you, regardless of what your CD4 count is. And we may not see those differences right away, but I think over time, these studies are telling us that it's not good to have viremia, and that we should be focusing as much on suppressing viral replication as we do on preventing immunosuppression.
Myles Helfand: We're just three months removed from the latest iteration of the U.S. DHHS [Department of Health and Human Services] treatment guidelines for HIV-infected people. That most recent update included an adjustment to the when-to-start recommendation. Now the recommendation is that if you're between 350 and 500, you should start therapy. Although, in what may have been a first for the guidelines, they actually specifically state that the panel was split over the when-to-start issue.
Does the research presented at CROI, and other research that's come to light over the months since those guidelines came out, do they just add to the amount of evidence that may further sway members of the panel in the future to go more towards, "You know what? Maybe we should start therapy even higher."
Joel Gallant: First, let me just spell out what the guidelines say now. Everybody agrees that you should start below 500. The split there was only about whether people felt that it was a strong or a moderate recommendation. It was just a split on emphasis. Below 500 is where we recommend therapy overall.
But then half the panel felt that we should recommend therapy above 500 -- in other words, at any CD4 count. The other half of the panel didn't think that was wrong, necessarily, but they just felt that it was more optional. So that was where the split was.
But I interpret this to say that the guidelines now support treatment at any CD4 count, but just with a different sense of urgency, based on where your CD4 is. If it's very high, then it's less urgent. The lower it gets, the more urgent it is. And I certainly think that the stuff presented at CROI only supports that.
I can't say whether it will cause a change in the guidelines. I think that most likely the when-to-start issue will take a rest for a little while, before coming out with yet another revision so quickly. But I certainly think that the stuff we heard is supportive of what the guidelines panel came up with.
Myles Helfand: There were some other presentations at the conference on life expectancy and mortality, and how they relate to CD4 count also, no?
Joel Gallant: Yeah. There had been a nice study a while ago from the Aquitaine cohort in France that basically said that if you achieved a CD4 above 500 and you had an undetectable viral load, and you maintained this for, I think it was, five or six years, your life expectancy was essentially going to be that of the HIV-negative French population. That's a study that I cite a lot to my patients, because so many of these life expectancy things, they'll kind of say, well, overall, you can expect "this many" years of life lost if you have HIV. I don't find that very helpful to an individual patient, because it includes the data from people who don't take their meds, who have hepatitis C -- all sorts of things. And if my patient isn't like that, then they can't really use those data to look at their own expectation. Whereas I think if you narrow it down, as the Aquitaine cohort did, to patients who are doing really well, I think that's very useful.
At CROI, we saw data from the ATHENA cohort, which is the cohort from the Netherlands, which modeled life expectancy for patients who were treatment naive and without AIDS 24 weeks after diagnosis. And again, they found that their life expectancy was around 53 years, which is essentially the same as uninfected controls in the Netherlands.
The French data and the Dutch data say that you can have the same life expectancy [with HIV as without it], under the right circumstances. The question then is: Will your quality of life be the same? Or will you be plagued with complications of aging at a younger age than HIV-negative people? And that's, I think, where the real question lies.
Myles Helfand: As a clinician, how do you talk to your patients about that kind of thing? How do you answer the, "How long will I live? And how well will I live?" questions?
Joel Gallant: I tend to tell patients that if you are starting therapy; and if you're good at taking therapy, you're not missing doses, you're not becoming resistant; and we can get your CD4 count up, that you can expect to live a normal life and die of something other than AIDS. Of course, I can't predict somebody's life expectancy. But I can probably tell them, "You're not going to die of AIDS."
The real question, as I said, is to what degree HIV-related complications will affect your life, even though you're doing well from an HIV standpoint. My own opinion is that if you start early enough, at a high CD4, you can probably avoid a lot of those complications. But what I don't know is whether you can avoid them all. I think that's the real hard question right now, the one we need to deal with the most.
So much of our data come from the practices of earlier years, where we did wait a long time to start therapy. If we started everybody with high CD4 counts -- and that's assuming we can find them at those counts and get them into care -- perhaps we would see fewer complications. That's my hope, as an optimist. But clearly, there is some residual inflammation and immune activation going on, even in people who are fully controlled. So we can't promise people that everything will be just as it would if they were HIV negative.
This article was provided by TheBodyPRO. It is a part of the publication The 17th Conference on Retroviruses and Opportunistic Infections.
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