July 18, 2012
Myles Helfand: This is probably also an important reminder for all of us that connecting a patient to relevant services, support services and education services, is so critical in HIV. In many cases, it's more than just going to your HIV physician every three to six months and getting a viral load test and talking about your health. It is also being able to be connected to the level of care that can get you educated more about HIV and its treatment, that can maybe get you some help for depression if you're experiencing it, to get help with unstable housing if you're experiencing it, to get help with just taking care of your loved ones and your family if you need it. The kinds of things that can be a barrier to starting therapy in the first place.
Paul Sax: Absolutely. One thing that's interesting: We were doing a quality assurance program, and we got a look at the proportion of patients here who are prescribed ART. I can't remember whether it was 93% or 91%; most of the patients in our clinic are either on therapy, or prescribed therapy. And that actually was reflected in a national study that was presented at CROI this year. So, among people in care, we're already very close to treating everybody.
Another way we know that anecdotally is because the basic science researchers we collaborate with are always looking for people not on treatment to help their pathogenesis studies along; they're looking for specimens. And it's getting harder and harder for them to find them. I'm sure this situation is similar at Hopkins.
Joel Gallant: Yeah, exactly. If you look at the CDC [U.S. Centers for Disease Control and Prevention] studies that have shown anywhere from 19 to 28% of Americans with HIV have undetectable viral loads, the problem is not that they are in care and not getting drugs, or that they're on drugs that aren't working; the problem is, they're not in care, or they're not diagnosed. That's where our gap is.
Once people are in care, they tend to get put on treatment and they tend to suppress their viral load.
Paul Sax: Exactly.
Myles Helfand: Speaking of getting on treatment and staying on treatment: Structured treatment interruption used to be a fun topic of much discussion and debate. Earlier in the last decade it fell apart, due largely to the findings of the SMART study, but also due to the increased potency and decreased toxicity of existing treatment, making it less likely that a person would want to stop.
There have been a few studies that, over the last year or two, have started to explore in more detail the idea of starting treatment during acute infection. These are people who start treatment immediately in order to achieve a level of viral suppression, maybe a stabilization of CD4+ cell count. Then after, say, six months or a year, they stop treatment for at least a few years to reduce the risk of long-term toxicity.
How do either of you feel about that approach? Is there any merit to it? Or do we just not know enough yet to be able to recommend that as an actual approach to treatment?
Joel Gallant: I'm not too excited about it. There is some evidence that early therapy, right after acute infection, may delay your need for antiretrovirals later. But we were doing a study like this, and when the time came for people to stop, they were often doing extremely well. They had high CD4s; they had undetectable viral loads; they were having no side effects; and the idea of stopping made no sense to either the patient or the clinician.
I think that treatment interruption studies are a remnant of the days when all we cared about was keeping your CD4 above a certain threshold, and nothing else mattered. Ever since the SMART study, we've realized that there's more going on than just CD4; that rebound viremia is not good for you.
So, for me: I just don't see the point of interrupting therapy that's working.
Paul Sax: Yeah. Those studies that you refer to, Myles, are interesting: Two randomized clinical trials for acute infection, where you had strategies in interrupting therapy.
I would be very surprised if any such study could be started today, simply because interruptions have consistently been associated with more harm than good. And there's no reason to really think why acute infection would be necessarily different from chronic infection, in that regard.
So even though, yes, there was benefit from treatment, as compared to no treatment, I bet you the benefit would have been even better if they had stayed on treatment. Believe me, and getting back to what you were saying before, we understand that these treatments, even though they're safer, they do have side effects. One of the big challenges in HIV medicine is managing the long-term side effects of these treatments, and knowing when is the proper time to consider a change, even with virologic suppression. But that's a whole different topic.
Myles Helfand: Yeah. That's a topic for another day, unfortunately.
So, where do we go from here? We used to refer to the debate over starting treatment as a pendulum that, for the better part of a decade, had felt like it swung in one direction against the initiation of therapy, due to toxicity issues and resistance concerns. And now, we are about as far in the direction of, "Yes, go ahead and start treatment," as we have ever been.
Are we done swinging back and forth? Looking into the crystal ball, where do you guys think you might be headed, in terms of when to start? Dr. Gallant?
Joel Gallant: I think the pendulum's done swinging. But then, you always think the pendulum's done swinging. You always think that what you know now is what's correct. And then you can be surprised sometimes.
The one thing that's out there that we don't know about yet is the START study, which is a randomized, controlled trial of when to start -- of earlier versus somewhat delayed therapy. Many people really objected to the guidelines moving in the direction that they did, without the data from the START study. They said that this would discourage participation in the START study.
While that may be true, I think the guidelines needed to do exactly what they did. Because the guidelines panelists felt that the information was sufficient to make these recommendations. And it would have been unethical to withhold that recommendation just for the sake of one study.
What happens if the START study shows a benefit to early treatment? Well, that will just confirm what we've already done.
What happens if there's no difference between early and delayed therapy? I don't think that will change people's minds. Because many will say, "Well, the benefits are long-term benefits. You're not going to see them in a trial, where your follow-up is, you know, six years." And in addition, it's not going to be measuring transmission.
It seems unlikely that the START study is going to show worse outcome with early therapy. If that happened, that would be a game changer. [But] I'm pretty comfortable that we're going to stay where we are.
Paul Sax: One issue that has come up with the START study is the question of how representative it is of patients in practice. That's because, when you look at the subset of people who are both (a) willing to be randomized and (b) cared for by providers who are going to randomize them or refer them for randomization, it may not be similar to the overall group who's out there.
It will answer some questions, no doubt. I think it will be fascinating to see what it shows. But it may not be the last word on this.
The other thing is, getting back to this cost issue: One thing that will be happening over the next few years is increasing availability of generic HIV medicines [in the U.S.]. Just like treatment of hypercholesterolemia becomes less expensive when statins go off-patent, the same will happen with HIV therapies.
Myles Helfand: At the same time, though, we have new therapies that are going to be approved. As of this recording, we've got the "quad" drug that's right on the horizon that is going to have a pretty long patent life, even as existing first-line meds -- like efavirenz [Sustiva, Stocrin], for instance -- come off their patent within the next 12 to 24 months, probably. To what extent do new drugs, like the quad, change the conversation at all?
Paul Sax: The safer and more effective the initial intervention, the easier it is to start treatment. Clearly, we need longer-term data on the quad and more clinical experience after approval, assuming it is approved, to say that that's the answer.
But for some people, they don't want to take a medication that has any CNS [central nervous system] side effects, like [those sometimes caused by] efavirenz. Or they may have a viral load that's too high to go on a rilpivirine [Edurant]-based treatment.
There's no perfect treatment out there. Obviously, if the medications were perfect, then everyone would be on treatment. It's moving the field forward incrementally, giving these new options.