Cal Cohen, M.D., is a SMART study investigator, and is the research director of the Community Research Initiative of New England.

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What do you think is the most important news to come out of CROI?

Well, certainly the biggest study to come out of CROI was the SMART study, and it was part of a whole seminar in which we took a look at STI [structured treatment interruption] trials for the past five years. And we took a look in the mirror and said, you know, well, we're making progress. And I think we could summarize that session pretty easily, which is: We see the potential for harm in treatment interruptions. The question is: Is there enough potential for good to continue to work with this concept? And I think that the short answer is that many clinicians are still trying to figure out the safest thing to do next, given all this data. To say that when people stop [treatment], sometimes bad things happen.

Is it the starting and stopping that's the problem? Or the low CD4 count baselines?

There are a couple of possibilities. One thing, however, that we know, is that the lower your CD4 is, the worse off you do. But in SMART, as Wafaa El-Sadr [one of the principal investigators for the SMART trial] was describing, even at higher CD4 counts, stopping [treatment] had risk. So while CD4 counts are relevant, there's also an additional contribution to HIV. HIV creates havoc; it is bad for us. And while most people do fine, some don't. And I think that's the question: How bad does it have to be, if HIV comes back, for us to say [the interruption] is worth discouraging, rather than recommending? And I think that's kind of where the field is struggling. Which is: What do interruptions get us? What benefit does it get, other than addressing pill fatigue? And if it's pill fatigue, are there better ways to address pill fatigue that are safer than a complete treatment cessation?

There are a few things that people are working with to try to understand it. Shorter interruptions, in addition to higher CD4s. Simplifying the pills -- you know, one pill a day. Therapeutic vaccinations so that you don't have to take pills. I think that the field has got the message, which is, people don't want to take pills every day. But I think we also got the message, which is that simply stopping [treatment] can be bad.

What does this mean for a patient who is currently on an interruption? Or a clinician who has a whole bunch of patients on an interruption? Should they rush them back on treatment? Or is it OK to remain on the interruption, if they're doing well?

Well, I think, in our study, "are doing well" is the question. Because unfortunately, when bad things happen, sometimes it's a surprise. So I'm well now; what will happen in six months? And again, in our study, in the SMART study, what was pretty clear is the longer you were off [treatment], the more likely that something could go wrong. So that doesn't mean there's a rush. Certainly there's no sense that, oh, my God; tomorrow something's bad. There's no reason to predict that. On the other hand, there's also this kind of random uncertainty to it. I think it's pretty clear HIV does create badness. The more of it you have, kind of, the more risk there is.

I think that the key piece, though, is that people sometimes do things even though there's a risk of harm. People smoke. People don't always buckle their seatbelt. There are things we do in which there is a chance for badness. This is just another one. People have to make up their own minds. If being on meds is worse than the risk of being off meds, then don't take meds. I think what the study does is it informs that decision with much more clarity, but it doesn't tell you what to do. It just says, here's the risk of being off [of treatment]; here's the benefit of being on. And people have to say OK; that applies to me. Or no: For me, being on [treatment] is just not what I want. People take the risk. People take risks.

What do you think of atazanavir as monotherapy? Do you think that it was a big dramatic presentation at this conference?

We saw atazanavir monotherapy at the conference last year, at the Rio conference. And I think, certainly, that presentation of that data was remarkable. I would think, personally, that it was the most surprising outcome of all, if only because we [had previously] understood that a single mutation would be enough to undo the benefit of atazanavir. And [that] single mutation drugs don't work as monotherapy -- before this. And so it clearly taught us something about boosted PIs [protease inhibitors] and how they are different. I think that we now have a second cohort [Susan Swindells' presentation] at this meeting, as you say, that worked. And it worked in almost everybody, with one exception. So, I think it's pretty exciting. And I think now the field, as Dr. Vernazza pointed out at the microphone, has to be careful to just understand: Is this working everywhere, or are there CSF [cerebrospinal fluid] compartments in which a PI isn't enough? What's the downside of adding the nucleoside to know that this [monotherapy] is worth doing? But I think, as the beginning of the story, it's a great, great story to understand, and to make sure that we understood what to do with it.

My final question is about integrase inhibitors. Do you think that was a big story, also?

We knew late last year how good the Merck integrase was; an almost 2 log drop as a median was terrific. No doubt that integrase, as a class, is on the ascent. Today we saw the second Gilead integrase: A 2 log drop at a couple of different doses, including a once-a-day dose. So it's great. Wonderful. It's tremendously exciting to see, in a heavily [treatment-]experienced population, over half of the patients [had CD4+ cell counts] less than 50, in a background that doesn't look like it's doing all that much. So it's tremendously exciting. I think now we enter that kind of zone of just making sure what problems there are, if there are any. The safety data that they presented showed that the short-term data are great. What the long-term implications are, we're going to be watching. But if this drug class continues to deliver, based on the two drugs we now have, integrases are going to be a very important drug for the next several decades.

For more information about the SMART trial, click here.