Is the AIDS Epidemic Over?

       Jon Cohen ends his thoughtful piece about the euphoria accompanying the introduction of the protease inhibitors with the injunction, “recork the champagne.” I guess it depends on whether you celebrate when you see the glass as half full rather than half empty.
       It’s worth toasting–while staying sober, of course–several unique advances marked by the successful development of these new antiviral agents. One is so-called “rational drug design.” The protease inhibitors came about through the use of high-performance computers, which analyzed the 3-D structure of the viral enzyme. The computers then screened tens of thousands of chemical structures, simulating those which acted as blockers. When tested with real virus and vulnerable T cells, the computer-designed molecules worked. It would likely have taken decades to identify these new drugs by the traditional approach of in vitro trial and error. This paradigm will be followed to develop other anti-HIV agents, targeting novel steps in the virus life cycle, such as initial attachment to the recently discovered chemokine co-receptor; insertion of the viral genes into the cell nucleus by another HIV enzyme called “integrase”; and the transport of viral genes out of the nucleus by the HIV REV protein to be packaged as new viruses. Each target, chemokine receptor, integrase enzyme, and REV protein can be studied in computer models, and then potential drugs selected. Another cause for celebration is the proof of principle that a clinical remission of AIDS is possible. Even in advanced cases, there can be striking improvement, with gain of weight and energy, and some return of immune function with reduced frequency of infections. If this can be achieved with the triple combination (albeit for unknown periods, as the article emphasizes), then adding still further obstacles to the virus in the form of attachment, integrase, and/or REV inhibitors will likely lengthen the period of remission and augment its clinical quality.
       An intoxicating message was broadcast by the media from the Vancouver Conference, seizing upon a hypothesis that HIV may be “cured” in select patients with triple-combination therapy (a hypothesis far from proven, or even likely) and representing it as the impending end to the epidemic. I’d be interested in Jon’s views on what caused this. Should scientists be more judicious in their presentations, knowing that the press is always anxious for a “hot” story with a sound-bite bottom line? And are David Sanford and Andrew Sullivan really culpable for buoying themselves with hope? Their hope is genuine–that time will be gained for them by the new drugs until more definitive treatments are developed that may conclusively change this from a fatal disease to a controlled condition.
       There is great biological variability in both the virus and its host. This is both a blessing and a curse. We expect that for some, the current remission may last long enough for them to enjoy the next generation of therapies, and a game of leapfrog–staying ahead of HIV–may be played into old age. For others, the wily virus will mutate and overcome the protease hurdles we have placed in its path.
       AIDS isn’t over. But we are at a new beginning in our understanding of how to potently inhibit HIV, and in our appreciation of how much clinical recovery is possible.