Hit early, hit hard" was yesterday's HAART mantra. Now, thanks to side effects and resistance, "Go slow" may be tomorrow's motto. But how slow is too slow? Federal bigwig Anthony Fauci, MD, said, "To strike a balance between adequately aggressive treatment and minimal adverse side effects, we need hard data."

That's why the government is funding the SMART (Strategies for Management of Anti-Retroviral Therapies) trial. And it's a big one. A network of community-based researchers, the CPCRA (Community Programs for Clinical Research on AIDS), will enroll 6,000 HIVers who will be monitored for an average of seven years. Half will be randomly assigned to the Viral Suppression (VS) group, where docs and their patients will be encouraged to use any and all drugs necessary to keep viral load as low as possible for as long as possible, following the current guidelines. The Defer or Delay Change (DC) half will be asked to hold off on HAART until their CD4 count goes below 250 -- a point, according to the University of Minnesota's Carlton Hogan, MD, one of the SMARTies who designed the trial, high enough so that opportunistic infections are unlikely but low enough that, if HIVers remain untreated, problems will develop in a year or two. "The hope is to ensure patient safety in the DC group, while sparing drugs for as long as possible," he says. If CD4s bounce back above 350, DCers will be encouraged to drop the drugs again -- until CD4s fall back to 250.

Comparison of early/continuous vs. late/intermittent will clarify the current quandary on when to start HAART, when to switch and which factors predict disease progression and the rates of side effects. Then we can all SMARTen up.