You could have heard a pin drop!” Well, in a hall seating hundreds of AIDS researchers and activists at San Francisco’s Seventh Conference on Retroviruses and Opportunistic Infections, this certainly wasn’t the case. But what is true is that that hard-to-please crowd erupted into applause  when—after years of big talk about hitting the virus with drugs and little attention to the side effects—William Powderly, MD, a leading AIDS researcher at Washington University, gazed out at his audience and said, “The goal of antiretroviral therapy that we’ve all agreed upon is that we should maximally suppress, with the best tolerated regimen, viral replication....That has become the mantra.... But that is not the goal of treatment. The goal of treatment is that we prolong meaningful survival for our patients.” Behind Powderly was a giant projection of a Star Trek–like spaceship and Mr. Spock’s famous motto, adapted: “(Let your patient) live long and prosper.”

And therein lie the rubs. At the symposium on HAART side effects at which Powderly was speaking, and in hundreds of scientific posters, there was an overwhelming barrage of information on drug toxicities—neuropathy, muscle inflammation, pancreatitis, liver problems, lactic acidosis, fat redistribution, insulin resistance, elevated blood fats, osteoporosis and more. Along with that list came the admission that there’s an immense amount we don’t yet understand about these side effects. We don’t know how many HIVers have them, or what causes them, or how they work, or, perhaps most pressing, what the long-term consequences are. In other words, no one can tell you what your risk is of getting sick or even dying from HAART-induced heart disease, diabetic complications or bone fractures from osteoporosis. All we know is that you have some risk.

That’s one rub. The other is, at what point are HAART-takers who have such problems no longer experiencing meaningful survival? And while that call is up to each HIVer alone, aren’t these consequences serious enough to make us take another look at the current guidelines trumpeting early intervention with these potent but toxic drugs? (See “Put Up Your Nukes”.) Powderly’s conclusion, reflecting a sea change in medical opinion, was a much-appreciated yes.

Call it the new treatment conservatism. Since the two great hypotheses on which the hit-early-and-hard strategy was based have proved false—combo therapy doesn’t totally stop the virus in a manner that affords a cure, and damage to the immune system isn’t irreversible—we must consider with great care the consequences of treating people for a very long time with drugs that have so much potential for harm.

“And therefore,” Powderly said, “we should be asking whether somebody who has no symptoms and no immediate risk of clinical progression should be exposed to these drugs at all, or at least not until they need them.” Based on chatting in the hallways and schmoozing at the hotels, it would seem that many researchers agree with Powderly, and that many clinicians have already adopted more conservative strategies when it comes to initiating treatment.

Powderly offered up another once-heretical notion—that structured treatment interruptions (see “Happy Holidays?” in POZ, December 1999 for more about these planned drug holidays) might provide not only improved immune responses to HIV, but also maintain the CD4 count at a safe level while minimizing exposure to toxic drugs. He cautioned, however, that STIs are potentially risky and require much additional study.

Then, voicing what was the unspoken theme on many minds, Powderly called for the design of new studies “that address the issues of using drugs for life or, if not for life, at least for a very long time.” And he closed with what could serve as the new message for the new age: “We need to figure out what is the right way to treat patients with antiretroviral therapy. Not for the short term but rather for the long—and hopefully successful—haul.” Amen, brother.