Prior to the availability of protease inhibitors and powerful three-drug combinations in 1996, it was common for people living with HIV and activists to talk about fighting for "The Cure." Along with the new drugs came excited talk about the possibility of eradicating or completely eliminating HIV from the body. Together, the new drugs and the hope of eradication mistakenly led many people to believe that The Cure had either been achieved or was just around the corner. Activism for The Cure all but disappeared.
Over time, we learned more about the limits of currently available therapy, and each new scientific conference told us that the goal of "eradication" was several more years away. Best estimates today suggest that for most people, it would take more than 60 years of near-perfect suppression of HIV to completely eliminate the infection -- a goal that few people see as attainable. In the meantime, people learned of the complex array of side effects that was the darker side of the new anti-HIV drugs, ranging from changes in body shape to heart disease.
The pendulum of expectations for The Cure rapidly swung from excessive hope to exaggerated despair, a cycle that has been repeated many times in the history of AIDS research and activism. With so much recent attention devoted to drug side effects and development of resistance, the word "cure" seems to have fallen from our vocabulary.
Will science ever be able to "cure" HIV disease? Perhaps it all depends on the definition. If the only definition of "cure" requires eradicating all traces of HIV from the body, then most scientists would say a cure is unlikely in our current generation. We simply have no idea how to remove HIV from our cells once the virus' genetic material becomes entangled with our own.
One alternative is to find a way to selectively kill all cells infected with HIV, but to date, these efforts have proven too toxic to use. A few researchers are still trying to pursue eradication with aggressive 4- and 5-drug therapies, and perhaps a few others hope that we will someday get a miracle drug that will safely root out every infected cell in the body. Most scientists, however, find these goals little more than wishful thinking. Several have argued since the earliest days of HIV that once the virus becomes integrated into our cells, we will never completely get rid of it. This is the sobering truth for a number of other viral illnesses as well.
Still, there is hope if we use another definition of cure. If we define "cure" as a treatment or strategy that will allow HIV-positive people to live out a normal life span, without a need for constant medication or threat of disease progression, then there may be several ways to achieve this goal. How do we know this is possible? Easy -- because we have already seen it in nature.
A small percentage of people living with HIV have remained disease- and symptom-free now for more than two decades, without treatment and without suffering the loss of their immune systems. These are the so-called "long-term non-progressors," who make up somewhere around 3% of all HIV-positive people. While 3% sounds small, it might easily add up to 20,000-30,000 people in the U.S. alone.
Earlier on, scientists thought such people might have a weakened form of the virus, but that has not proven to be the case. Nor has any study found some common, personal element among the people -- the right diet, exercise, beliefs, etc. There's evidence of unique genetic factors in some, but not all such people.
Scientists are gradually concluding that their experiences are due to a stronger and more effective kind of immune response against HIV itself. Why some people have it and others don't is still a mystery, but if this is the mechanism that makes HIV disease all but irrelevant to their health, it gives us a profound clue about where future AIDS research must go. Other clues might exist in monkeys who can be infected by HIV but never become ill.
This pursuit of stronger HIV-specific immune responses is the goal behind some of the research into Structured Treatment Interruptions (see publications Wise Words #7 and PI Perspective 31 for more information). It is also the goal of recently renewed interest in using vaccines as a form of treatment for people already infected, called therapeutic vaccination.
The theory of using vaccines as therapy has been around for many years, but it's only now that we are beginning to see vaccines powerful enough to produce the desired effects. Improving the immune response against HIV itself is also the goal of many therapeutic strategies aimed at the immune system itself. Unfortunately, this field of research doesn't get nearly the amount of attention or funding as developing anti-HIV drugs.
One vision of future treatment strategy builds upon what is good about anti-HIV therapy, but then brings in new approaches to supplement and carry on for it. For example, a year's worth of strong antiviral treatment might be followed by a period off treatment coupled with the use of a therapeutic vaccine. The therapeutic vaccine might work best when viral load has first been suppressed by antiviral therapy. But the vaccine might have the additional advantage of causing long-term protection against the virus by the immune system itself. In contrast, the action of antiviral drugs stops rapidly once the drug is withdrawn.
Perhaps the immune response triggered by a potent vaccine might even be amplified by a drug like interleukin-2, which causes most types of CD4+ cells to aggressively multiply and appears to extend the life-span of these cells. If this effect occurs when viral levels are extremely low, and the anti-HIV immune response is being stimulated, it may be possible to trigger a condition similar to that seen in long-term non-progressors.
This is but one possible scenario for upcoming research. But there is a growing sense that we have achieved all we can with anti-HIV approaches and that the next generation of research must seek to better harness the immune system. In effect, treatment will mean training the immune system to do a better job fighting HIV, just as we know it is capable of. If the outcome could be indefinitely long periods without a need for anti-HIV therapy, and thus without their side effects -- perhaps boosted by periodic vaccinations -- one reasonable definition of "The Cure" might be achieved.
How long will this take? It's just a guess, but perhaps within five to ten years we will know if this strategy is taking us in the right direction. It may be that one or another of the elements of it -- treatment interruption, therapeutic vaccination, or direct immune based therapy -- will prove useful, or that one or all will fail.
It's impossible to predict the future. Uncertainty is always present. But the general theory of modeling our search for a functional cure on the example of natural control of HIV infection is almost certainly a wise pursuit that seems far more likely to succeed than an endless series of slightly improved antiviral drugs.
Although a cure for HIV is not clearly in sight at the moment, we need to continue working toward it and remembering that it is, overall, our most important goal. And, as always, hope and positive thinking, along with well-targeted activism, will play a critical role in getting there.
Back to the Project Inform WISE Words July 2001 contents page.