The Bright Power of 'Negative Energy' in AIDS Research
The Role of HIV-negative Volunteers in the Fight Against AIDS.
by Charles Gonzales, MD

New York City has the largest number of HIV-negative AIDS study volunteers--- more than anywhere else in the United States. This is not a misprint. It reads correctly: HIV-negative study volunteers----people who are not HIV positive. People, who do not themselves have an HIV worry in the world. Individuals who are not themselves infected with the HIV virus but obviously affected by AIDS. Affected enough to volunteer to fight AIDS and help find its cure. The number of people who have volunteered is truly amazing. They are a true testament to what is right in the world. Their motivation is as varied as New York City, their commitment staggering. Where others run away from the image of AIDS and see "risk-groups", these volunteers see their daughters, brothers, cousins, dear friends, and high-school sweethearts as well as looking out across the sea to our common humanity. When it comes to AIDS, these folks are indeed thinking globally and acting with their hearts, minds and bodies locally. They can and should be rightfully called heroes, literally giving their blood, in the war on AIDS.

And the war on AIDS cannot be fought and will never be won without them. Here's why: No drug or vaccine currently in development to combat HIV is ever used in someone who is HIV positive, without it first being tested in someone who does not have the virus in their system. The reason is simple. The HIV virus causes subtle changes in the body----as we all now none of them good---so in looking for the potential dangers or complications of a new treatment, it is much safer to remove the possible complexities of the virus itself from the mix. In this way, if there is an unusual reaction or toxicity, we know it can only be the treatment and not the HIV virus that is at fault. HIV negative study volunteers have not only had these new drugs tested on themselves first, but have also continued to volunteer and help learn how these new drugs interact with the approved medicines already in use in the fight against HIV.

The greatest needs and challenges in HIV research today are creating safe and effective vaccines against HIV. Drugs alone will never be enough. We must have vaccines. We know at least two types of vaccines are needed: a preventative vaccine---a vaccine stopping HIV transmission and preventing new people from becoming infected, and a therapeutic vaccine---a vaccine which will cure or control HIV in someone who is already infected with the HIV virus. In this, the greatest challenge we have in the fight against HIV, HIV-negative volunteers are crucial. Even though these vaccines are not dangerous, HIV-negative volunteers are essential, indeed vital, in their development. A working vaccine cannot be developed without them.

All vaccines essentially work by tricking or alerting the body's immune system into believing a small, innocuous and harmless fragment of a pathogen, such as a virus or bacteria, is the whole virus or bacteria itself. In this way, when the virus or bacteria actually does try to invade the body, the immune system is already revved up and primed to attack. The HIV virus causes immunodeficiency---AIDS, as we all know---by destroying the very T cells, the body needs to recognize and fight invading pathogens. What remains an enormous stumbling block, which must be overcome to create an effective cure, is how and what part of the HIV virus allows it to camouflage itself when it first enters the human body.

Early on, the HIV virus prevents the immune system from seeing, reacting and controlling it, the way the immune system ordinarily does with any other pathogen. The immune responses and often equally as importantly, the lack of immune responses in these HIV-negative vaccine volunteers allows us to understand and overcome this initial immunological blindness caused by the HIV as it first sets-up shop in an HIV infected person.

The aim of a vaccine against HIV is to alert the body's immune system that HIV is actually there. HIV-negative volunteers, in our HIV vaccine research trials, are presently helping us to do exactly that---figuring out what tag or part of the virus needs to be in a vaccine to alert the body's natural immune system before HIV can set up its T cell destroying virus making factories. With their normal and healthy immune systems, HIV-negative vaccine study volunteers allow us to study in the laboratory, what arms of the body's immune system---in the test-tube at least--are most effective in fighting HIV head-on. The current HIV vaccine trial at NYU-Bellevue using the Merck AD5 vector is based on just that: kind of pure biological information. The vaccine has been formulated to ingeniously elicit the immune responses that are believed to be protective in HIV-infected "Long-Term-Non-Progressors"; those rare individuals who are able to completely control the HIV virus without needing medications or getting sick and losing their T cells. These rare HIV-infected individuals did something immunologically right when they were first confronted with HIV: they treated the HIV virus like any other invading virus and quickly brought it under control. The current HIV vaccine study, in our HIV-negative study volunteers, appears to be doing just that, mimicking those broad anti-HIV immune responses that appear necessary to control HIV. Our HIV-negative vaccine volunteers are still helping us determine how long these immunologic responses last and how often they may need to be boosted. A modified version of this vaccine (also tested first on our HIV-negative volunteers) will be tested as a therapeutic vaccine in HIV-positive people in the fall.

When the history of an HIV cure is finally written, HIV-negative vaccine volunteers will have a bold and prominent place. If you too would like a role in writing the history of ending AIDS, you are welcomed to join the hundreds of your HIV-negative fellow New Yorkers on our vaccine trials.