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Why has AIDS proven so difficult to cure?
HIV-1 has devised clever strategies that allow it to persist for many years in an infected person. HIV-1 splices its genes into those of the host, so it is intimately associated with a variety of cells. The virus hides in certain reservoirs in the body that are not easily reached by current drugs. Moreover, as HIV-1 spreads in an infected individual, it undergoes changes. Thus, many variants of HIV-1 can exist even within a single person.
"The work of several DFCI laboratories has the potential to strengthen the immune system's response to HIV-1.
— Joseph Sodroski, MD, director, Center For AIDS Research
This variation allows HIV-1 to escape from the patient's immune system or from some antiviral drugs. We're not treating one virus, but many thousands of slightly different viruses, each tenaciously integrated into host cells. A realistic goal for the treatment of HIV-1-infected individuals is not to totally rid the body of HIV-1, but to suppress it so that it does not cause disease and is not efficiently transmitted to anyone else.
Despite the fact that an enormous amount has been learned about the AIDS virus and how it undermines the body's immune system, there still is no vaccine or cure. What is left to uncover?
We shouldn't underplay how far we've advanced from the early 1980s. At that time, there were only one or two drugs useful against any virus. Today, we have more drugs active against HIV than against all other viruses put together — largely as a result of intensive research. Because of these drugs, people with HIV-1 are living longer, more productive lives.
We have exquisitely sensitive tests to detect HIV-1 and to determine whether a person or blood sample harbors the virus. This ability has led to the near elimination of HIV-1 from much of the world's supply of blood products. A disaster of enormous proportions was thus averted.
There is much left to be done. The drugs developed so far target the more vulnerable parts of HIV-1, but there aredozens of other potential targets on HIV-1 that will probably be more difficult to tackle. We need to understand the molecular details of these targets if new kinds of anti-HIV drugs are to be developed. Continued commitment to research is required to stay one step ahead of this everchanging virus.
It's often said that the best hope for AIDS patients in poor countries is a vaccine. How close or far are we from such a vaccine?
Treatment of HIV-1-infected people is expensive, must be continued for many decades, and has a variety of difficult side effects. To date, such therapy is available primarily in industrialized countries. Most HIV-1-infected people live in the developing world. We should make efforts to provide treatment options to HIV-1-infected people in poor countries for humanitarian reasons, but economic realities suggest that these expensive approaches probably won't have a long-term impact on the AIDS epidemic. In the same vein, educational efforts encouraging safe sex and needleexchange programs are worthwhile, but the only realistic way to change the course of the epidemic is a vaccine that prevents people from becoming infected.
The challenges facing an AIDS vaccine are considerable. We've never made a vaccine against a virus that persists for long periods of time in an infected host, even when the immune response is doing its best to rid the body of the virus. HIV-1 has tactics that allow it to evade an immune attack and eventually destroy the immune system.
We've learned a lot about how a stronger immune response to the virus might effectively suppress HIV-1. But we still need to learn how to generate such immune responses in safe ways, and that will require extensive research into the interaction of the virus and immune system. The vaccines currently used in human clinical trials, as well as in trials planned for the near future, are not expected to provide optimal protection against the virus. These represent our first forays into what will be a long and difficult endeavor. Intensive research on HIV-1 itself and immunology in general will be needed over the next decade to fuel new vaccine ideas.
What has research into AIDS taught us about the human immune system and how it works in fighting diseases? How can we apply this knowledge to treating other diseases, including cancer?
Support for AIDS research has stimulated many new insights into the normal state of the immune system, and into the system's ability to respond to an invader that changes over time. This knowledge is highly relevant to a variety of research problems, such as immune protection against other infectious agents or cancer cells. Researchers seeking to strengthen the immune system's ability to recognize and destroy cancer cells and virus-infected cells should benefit from these findings.
On a more specific level, HIV-1 depends on many host cell proteins to reproduce and spread. These include receptors on the cell surface, proteins that control what enters the nucleus of the cell, and proteins that switch genes on and off. In several cases, we never knew such proteins existed until researchers found they were useful to HIV-1 and studied their function in normal host cells.
Several of these cell proteins have turned out to be involved in cancer, autoimmune diseases, cardiovascular disease, and nervous system disorders. No doubt, as the human genome is fully deciphered, more connections will become apparent.
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