So it's official. The "cure" isn't the cure. That most publicly posed of questions -- Can HIV be eradicated? -- now has an answer: No. After the disappointing findings of three major studies published last November, the verdict is in: Whether driven by cynical manipulation or misguided good intentions, eradication is a fantasy.
How we wanted and needed to believe! Yet no sooner had Dr. David Ho, the toast of Vancouver and Time's 1996 Man of the Year, tantalized the planet than his ever-elusive cure began to fade. With each passing season's scientific conference, it slipped further from our grasp. Early last year, Eradication Inc. declared two to three years' treatment enough to wipe out HIV infection; by spring, it was six years; last fall, a decade or more.
And then the model imploded. Buried in the footnotes to the headlines of therapeutic euphoria were two fundamental preconditions: That the current cocktails shut down viral replication 100 percent in all parts of the body, and that the cells already pirated by the virus grow old and die before the patient does. Neither is true.
Taken together, the three studies -- each by a leading researcher -- report ongoing, low-level viral replication, the persistent presence of infectious cells and at least one type of infected CD4 whose numbers never so much as dwindle. Even in someone whose viral load has been undetectable (less than 200) for 30 months, the virus lives on; stop therapy, and -- at least in the lab -- it can return, raging.
If the cure doesn't exist, what is to be done? Is it time, once again, to charge our credit cards to the limit? Or can life go on without eradication? Experts disagree. Hard-nosed realists argue that viral eradication was never even a possibility. "Can HIV be eradicated?" was the wrong question, they say. These determined empiricists have maintained all along that HIV infection is forever. A more realistic scenario would be to maintain HIV at levels low enough to spare the immune system and allow the virus and its host to peaceably coexist -- with or without treatment. Follow this line of thought, and the apotheosis of eradication sacrifices the lion's share of its mystique.
Eradication or not, nothing in the bleak ramifications of these three experiments in any way undoes the renewed well-being and Lazarus-like returns of thousands of PWAs over the past two years. Many who had a mere 10 to 20 CD4 cells in 1995 now have 200 or more. And with viral loads dramatically reduced, once-ravaged immune systems can now function at a satisfactory level. But with the twilight of the eradication ideology, it is doubtful that the current rush to treat is in the long-term interest of asymptomatics with a moderate viral load and an intact immune system. For anyone who has not yet bought a ticket to the triple-cocktail lottery, waiting even six to 12 months to embark upon this uncharted pharmaceutical odyssey may make a world of difference: This year we may finally figure out what harm and good these drugs are actually doing and have regimens that are easier to start and stick to.
For the hordes who have already succumbed to the pressure to "hit it early and hard," it's more important than ever to take this pill-popping business seriously. But the bravest of the lucky ones -- those with "undetectable" viral loads for 12 to 18 months or more -- might consider a leap off the edge of the known treatment map into "subtraction" therapy: Reducing or switching a three- or four-drug combo to a two- or one-drug regimen. The idea -- highly speculative -- is that once the virus has been brought to its knees, a less aggressive assault may keep it down. Toss out the protease inhibitor (or the 3TC) before resistance develops, and you may be able to use them in the future.
While right now the drug pipeline is as empty as Mother Hubbard's cupboard for all but antiretroviral virgins, there are enough new approaches for a scintilla of optimism. The pleasant surprises of the eradication era have infused us all with a new energy that we mustn't lose. If the antiretroviral approaches have taken us as far as they can, so be it: Now immunological and cellular approaches must carry us the rest of the way. With vigilance and advocacy, these therapies could be available in a year or two. All we have to do is stay well until then.