July 17, 2003

Ed Susman

July 17, 2003 (Paris) — Researchers found disappointing results in a trial that investigated structured treatment interruptions, the controversial option designed to give patients relief from complex daily drug regimens.

The results of the Staccato Trial showed that a week on, week off treatment interruption was associated with virologic failure, said Bernard Hirschel, MD, professor of infectious diseases at Geneva University Hospital in Switzerland.

According to Dr. Hirschel, 19 (53%) of 36 patients on structured treatment interruption experienced virologic failure within a few days or weeks after beginning the protocol.

In the study, 112 patients were randomized to one of three groups: (1) week on, week off, (2) a conventional continuous treatment schedule, and (3) an interruption schedule that monitored CD4 cell counts in determining when patients could take a drug holiday. The three groups were a substudy of the 433-patient Staccato cohort.

The week on, week off group of the study has been discontinued, but Dr. Hirschel said the other two groups of the study are continuing.

"Every doctor who has patients with HIV and every patient who is taking antiretrovirals has a friend or has heard of a friend who is doing well on interrupted treatment," said Michel Kazatchkine, MD, director of the National AIDS Research Agency in Paris, France. "But these regimens are not benign. And they continue to be controversial."

Dr. Kazatchkine, said, however, that structured treatment interruption is not yet ready to be scrapped, despite findings in Dr. Hirschel's study and others. "There are several ongoing studies in the United States, France, and in Africa testing various options in structured treatment interruptions."

"Structured treatment interruptions should only be conducted as part of a well controlled clinical trial," said Patrick Yeni, MD, professor of medicine at Hôpital Bichat-Claude Bernard in Paris.

In the SWATCH study, which was also presented in the conference's late breaker session, researchers said that switching patients from one regimen to another on a planned schedule appears to extend the effectiveness of HIV treatments. "It may be valuable to switch HIV regimens every few months, rather than continuing with one until it stops working," said Javier Martinez-Picado, PhD, from Hospital Universitari Germans Trias I Pujol, in Badalona, Spain.

Dr. Martinez-Picado's study was a randomized, open-label trial that compared the planned switching of regimens with remaining on a standard-of-care program until treatment failure. The study enrolled 161 patients in 15 centers in Spain and Argentina, and they were randomized to either of two standard-of-care groups, or an alternate-care group. The patients were treatment-naive and had a viral load greater than 400 copies/mL. One group of patients received stavudine, didanosine, and efavirenz; a second group of patients received the zidovudine, lamivudine, and nelfinavir. If patients experienced virologic failure, they were switched to the other group or to another regimen entirely. In the alternating-care group, patients were switched every three months between regimens, Dr. Martinez-Picado said.

Over the 48 weeks of the study, the time to virologic failure — the main outcome measure — was significantly delayed in the alternate-care group compared with the two standard-of-care groups. The data showed that 98% of patients in the alternate-care group had not experienced virologic failure compared with about 82% of those receiving standard of care ( P = .002). In addition, the percentage of patients with a viral load less than 400 copies/mL and less than 50 copies/mL was significantly greater in the alternating-care group.

There were no significant differences among the groups in terms of CD4 cell counts, frequency of adverse events, or reported drug adherence. In fact, Dr. Martinez-Picado said, adherence overall in the study was good.

Dr. Wainberg explained that by alternating regimens when the virus was suppressed by one regimen, introducing a second different and active regimen would continue to keep the virus at undetectable levels and still allow for doctors to switch back again without jeopardizing effectiveness or creating resistance.

Second IAS Conference. Presented July 16, 2003.

Reviewed by Gary D. Vogin, MD

Ed Susman is a freelance writer for Medscape.