January 17, 2006

SMART Doc Cal Cohen: Are The Med Holidays Over?

Last week, POZ learned that the three-year-old treatment interruptions study known as Strategies for Management of Antiretroviral Therapy (SMART) had discontinued its “no treatment” arm because of a higher incidence of AIDS-related events in that group. A full explanation and an analysis of the findings are still to come. But meantime, we checked in with Calvin Cohen, MD, one of the principle investigators in the massive study (6,000 subjects are involved) to find out how things went down—and what it all may mean.

POZ: How did this start?

Cohen: The [federal] Data Safety monitoring Board (DSMB) found signs that people in the off-treatment arm of the study were experiencing a small number of serious illnesses. The rate of these illnesses was significantly higher in the off-drugs group—about 3% compared to about 1.5% in the on-meds group. So we met to talk about how to implement their findings, what to do. The conclusion was to discontinue the randomized portion of the study [where some people get assigned to a group that doesn’t take meds at all]. Now we go into follow-up, observing what happens to people as they go from the no-treatment arm into treatment.  

POZ: Did these findings come as a surprise to you?

Cohen: Yes, the underlying assumption was that people on meds would do worse on things like heart attacks, diabetes, lipo, strokes—the grab bag of [HIV med side effect] complications. Instead, we found that in the first two years, there was a doubling of serious complications [among those off treatment] such as AIDS and other illnesses—including cardiovascular disease and metabolic problems.

POZ: Are you disappointed about discontinuing part of the study?

Cohen: No. We answered the questions we set out to answer. If treatment breaks are viable, they have to be safe. For many people they might be safe; for others, they’re not. What we wanted to know is if meds are better than the alternative. We’re in an era when the meds are improving. If you don’t feel well on the meds, you can try to find others.

POZ: But doesn’t this say that treatment interruptions are a bad idea?

Cohen: The study doesn’t say that people must be on meds. It does say, “If you’re thinking of coming off meds, we can say there is a risk of events with low frequency but high danger. In that light, staying on meds might not be such a bad option.” This doesn’t change the fact that some people do fine off meds. That’s still true. But what we learned is that we can’t predict who is going to be fine off meds and who is not. Until there’s a test to say who will do well, we recommend, “Stay on.”

POZ: What does this mean for your other treatment interruption study, “five days on meds, two off?” [This small study, also called FOTO, has been testing the 5-on-2-off pattern of dosing for certain HIV combos for about two years.]

Cohen: That study becomes more important in light of the SMART results. We felt that the approach of 5 days on meds/2 days off was successful. We just received a grant to do a randomized small trial in Florida and Boston to further validate that approach. Ultimately, if you can’t stop meds long enough [to allow your viral load to rise], maybe we can start and stop, as we do in the FOTO study.


To find out more about the FOTO study, contact Sandy Sheble-Hall at shall@crine.org or 617.778.5454 X238.