Who Is Looking for the Cure for AIDS?
The Government Has an Extensive Plan for AIDS Research, but Finding a Cure Is Not Part of it
Martin Delaney was a pioneering AIDS activist who believed that knowledge was strength and that hope was an essential ingredient in the fight against HIV. In that spirit he founded San Francisco's Project Inform in 1985 and dedicated his life to obtaining information and clearly communicating what he learned to people living with the virus. Perhaps thousands of people are alive today because they heard Marty Delaney speak at a town hall forum, or read one of his newsletter articles, and understood that treating HIV was possible, and that there was hope. Marty had seen the darkest days of the epidemic and he heralded the dawn when the first effective combination therapies were revealed in the mid-1990s.
Despite the triumphs and disappointments with what AIDS drugs could and couldn't do, Marty never lost sight of the ultimate hope: that one day a cure for AIDS would be found. While others dismissed seeking a cure as scientifically naïve, Marty continued to raise the issue whenever he met with the government, scientists, the drug companies, or with groups of people living with HIV.
Martin Delaney died of liver cancer in January 2009, but his hopes for seeking a cure no longer seem naïve. A few visionary researchers are finally starting to turn their attention to the supremely difficult challenge of eliminating or permanently defeating HIV in the body. It may take 20 years or more for curing HIV infection to become practical -- or even possible -- but the quest is now being taken seriously. And that is what is needed to keep hope alive.
Since the beginning of the epidemic nearly 30 years ago, the two great quests of AIDS scientists have been to develop a vaccine to prevent HIV infection and a treatment to cure it. Although combination drug treatment has proven able to stop HIV cold, it is not a cure, and drugs must be taken carefully and consistently for life or the virus will come roaring back. After great hopes and millions spent on finding a vaccine, science's best efforts have been disappointing, although the search continues. Yet, despite the thousands of scientists working to improve the lives of people with HIV, relatively few have taken up the challenge of curing the disease for good. While there are signs the quest for a cure for AIDS is finally gaining some respect, high level leadership is still lacking. Even the government does not rank curing HIV very high on its list of priorities for AIDS research.
The 200-page National Institutes of Health (NIH) Plan for HIV-Related Research1 for 2010 sets out the US government's priority areas for AIDS research and serves as a road map to coordinate its investment in AIDS science. The plan establishes two major priorities for NIH AIDS research: the prevention of HIV transmission and the prevention and treatment of HIV-associated illnesses and coinfections.
A glance at the plan's priorities makes it clear that finding a vaccine is a key goal of the NIH AIDS science effort. This is certainly justified given the enormous impact that a preventive vaccine would have on the course of the epidemic. However, if you search for mention of a cure, you will come up short. Attempting to eliminate HIV infection is not a priority, an objective, or even a strategy mentioned in the NIH plan. This gap in the national research effort raises a troubling question: How likely are we to find a cure for AIDS if it is not on the official road map?
One reason why curing HIV infection receives insufficient attention from the scientific establishment is because it has seemed like an extraordinarily difficult -- perhaps impossible -- goal to achieve; and research money tends to flow to problems that people believe can be solved.
There are two things that will make curing HIV infection so tough. The first is that HIV inserts its DNA into the DNA of an infected person's immune cells, and in some of these cells, the viral genes go to sleep, giving no sign that they are there until they are activated at some future point. This is called latency. Because modern antiretroviral (ARV) drugs can effectively prevent circulating virus particles from infecting fresh cells, latency on its own wouldn't be such a problem if all of the infected cells died off fairly quickly (cells that actively produce HIV tend to self-destruct after a short while; uninfected and latently infected cells survive longer). But some of the infected immune cells go into a "resting state" of dormancy, and may stay that way for ten years or longer. Others may divide and give rise to fresh daughter cells that carry a latent copy of HIV. This means that HIV infection is persistent.
Because HIV establishes a persistent and latent infection in very long-lived resting immune cells, a reservoir of HIV is created within the body that could potentially take decades to disappear -- and that's if the reservoir was never replenished by viruses that managed to escape the antiretroviral drugs. One of the lingering questions for scientists is whether reservoirs are replenished by active viral replication or not. In any event, if the drugs are stopped before the reservoir is fully depleted, then HIV will resume infecting new cells, and levels of virus in the body will surge.
The investigation of HIV latency and persistence does not appear in the short list of research topics that the NIH says will receive the highest priority under its plan for HIV research. Only a few lines in the plan call for studying factors that enable HIV to establish a persistent infection or for understanding the reservoirs that permit HIV persistence. It's no wonder that scientists who apply for funding to study HIV latency are so often turned down: the term does not appear in the NIH plan.
There are many good reasons to be skeptical about the chances for actually curing HIV. The mechanisms that permit latency are still not fully understood, and there are competing theories for how the viral genes are silenced in certain cells. In fact, there are likely multiple mechanisms at work, which means that any single approach to a cure could be insufficient.
In brief, the main theoretical strategies for eliminating HIV from the body involve:
The last of these strategies is the sci-fi approach and (despite a recent report2) may not be possible for many decades. Identifying latently infected cells and killing them sounds ideal, but how to do it remains a puzzle since, by definition, such cells look exactly like uninfected cells. Thus, a strategy of waking up the cells of the latent reservoir and getting them to start making HIV copies seems like a plausible first step. Once awake, the infected cells would self-destruct or be eliminated by the immune system; antiretroviral drugs would protect new cells from becoming infected; and, theoretically, the body would soon be free of HIV. This idea is thought of as "purging the reservoir" and a few early, though unsuccessful, trials have been attempted in people.
Research into how the reservoir of latently infected cells can be flushed out is proceeding slowly in a few laboratories around the world. But government support is needed to invigorate this research and put finding a cure for AIDS back on the map. Marty Delaney kept our hopes for curing HIV infection alive. Now it is time for all of us to demand that the quest for a cure not be forgotten.
Bob Huff is the antiretroviral project director at Treatment Action Group (TAG) in New York.
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This article was provided by Being Alive. It is a part of the publication Being Alive Newsletter. Visit Being Alive's website to find out more about their activities, publications and services.
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