Roll Up Your Sleeve
 After more than ten years and close to 12 million deaths, the dire predictions made about the AIDS epidemic in the early eighties have come true. Over 30 million people are infected with HIV and close to 5 million more will become HIV positive in the next year. AIDS was once seen as a problem for gay men and IV drug users, but is now devastating minorities and women. Outside of the developed world, the numbers of HIV positive are staggering. In sub-Saharan African countries like Zimbabwe, up to 25% of the adult population is HIV positive. AIDS is a plague on a global scale. According to Dr. Mark Mulligan, an AIDS researcher, AIDS is the polio of our generation, only worse.
 

 

The HIV Virus
Today, most people only know polio as the affliction that confined President Franklin Roosevelt to a wheelchair. At its peak polio kept children out of schools and public swimming pools, and disabled hundreds of thousands. Polio is a viral infection causing weakness in the limbs, paralysis and sometimes death. The sight of victims, often children, in leg braces and iron lungs terrified millions of parents in the 1950s. The March of Dimes was founded to fight the disease and support vaccine development efforts. Nearly 20,000 cases of paralytic polio were reported in 1952. 35 years later only a handful of cases are seen.

Steps in an HIV Vaccine Trial
1. Counseling and education, answer questions
2. Signing of informed consent forms
3. Screening (sexual history), physical exam, laboratory tests (HIV)
4. Enrollment, scheduling
5. Vaccination, 3-4 times over 6 months
6. Monitor safety and immune responses
7. Counseling and Education and Unblinding

The Salk vaccine, developed in 1955, and succeeded by the Sabin vaccine in 1961, brought polio under control. It is the hope of many that a similar vaccine approach might bring the AIDS crisis to an end. Indeed, that’s the goal of Dr. Mulligan, Director of the Alabama AIDS Vaccine Evaluation Unit (AVEU). Mulligan is part of a network of researchers from the National Institute of Health (NIH) and around the world, trying to apply hard won knowledge of vaccines against AIDS. This effort is directly supported by the residents of Alabama. According to Dr. Mulligan, “Since 1994 we’ve immunized 200 people. Around the country this network has immunized almost 3,000 people with prevention vaccines. The vaccines have been safe and well tolerated.” 

Billy Tingle administers a vaccination to yours truly, photo by Domino
How does a vaccine work? When the immune system is exposed to antigens, it can react and clear potential infections, viral or bacterial. Antigens are usually small pieces of protein from a pathogen, part of a bacterial cell wall, or in the case of a virus like HIV, part of the viral coat (or surface) proteins. Huge amounts of protein can confuse the immune system and cause problems, like allergies, but the right amount, in the right place at the right time, can alert and protect the body from pathogens it has yet to encounter.
Successful vaccine efforts include the control of polio, mumps, measles, and perhaps one day, influenza and chicken pox. Smallpox, which killed millions in Europe in the middle ages, has been completely eradicated. Only small amounts of the virus remain in a vault at the Centers for Disease Control (CDC) in Atlanta. 
  Modern vaccines are the product of genetic engineering or manipulation of the pathogen at a molecular level. Using viral proteins, DNA, or a modified canarypox virus, researchers hope to create an immune response sufficient to protect against HIV infection and disease. In the AIDS vaccine trial, the protein vaccines contain a protein that is part of the viral coat of HIV called gp120. Another candidate vaccine is the canarypox virus. This is an attenuated virus, which has been genetically altered and weakened. It delivers a small amount of DNA to target cells, which then briefly make of one of the HIV proteins. The canarypox virus cannot multiply, and indeed, its cycle of protein production is very brief. This virus cannot even make a canary sick. A third candidate vaccine is DNA itself. This DNA vaccine produces antigen by direct injection of DNA into muscle cells, which then briefly make the protein of interest, in this case, HIV proteins.
Unlike in the film “Outbreak,” vaccine production is a laborious, time consuming process requiring many trials and thousands of volunteers. In the early days, the Alabama AVEU reached out to the gay community. Volunteers are recruited and selected from the community and categorized as individuals at lower, moderate, or higher risk of acquiring HIV. For example, lower risk means having few sexual partners (4 in 6 months), and practicing safer sex precautions.

Katrena Johnson gets some vitals before taking some blood, photo by Domino

Volunteers must be in good general health, and HIV negative. According to Dr. Mulligan, nine of the first 10 AVEU volunteers were gay men. Today the program is striving to be representative of the AIDS crisis worldwide and is actively recruiting gay men, lesbians, women, and people of color.

The AVEU has been conducting both phase I and phase II clinical trials for four years. These trials measure the safety of a vaccine. In addition, these early trials measure the immune response, and allow modification of the protocol to produce the greatest immune response.
 Phase III trials measure the ability of a vaccine to protect an at risk population from infection. The canarypox virus protocol has shown some promise and phase III trials may begin within two years. A private company, VaxGen, led by Donald Francis (hero of “And the Band Played On”), is beginning in several US cities and Thailand, a phase III clinical trial of a candidate vaccine derived from the gp120 protein.

AVEU LInks:

CDC - Division of HIV/AIDS Prevention (DHAP) Home Page

AIDS Knowledge Base - Home

HIV/AIDS Information Center

AIDS Clinical Trials Information Service

The National Institute of Allergy and Infections Disease: NIAID DAIDS

Meanwhile, the AVEU continues to seek volunteers for many ongoing protocols. The volunteer opportunity is described by Dr. Mulligan this way “If you have a family member, a friend, a partner, significant other, who’s not infected; we have a program where they can help fight AIDS. That’s unique. Many opportunities exist to donate money or time, be a buddy, to help fight AIDS. This is a way to actually roll up your sleeve and be in a clinical study, normally an avenue only open to HIV infected people.”
 To recruit volunteers and administer the vaccination protocols, the AVEU relies on a full-time nursing and recruiting staff, Susan Duncan, Peter Bonventre, Billy Tingle and Catrena Johnson. They screen potential volunteers and educate about AIDS, safe sex and the vaccine concept. Some potential volunteers are concerned about the relationship between the vaccine and the pathogen, fearing HIV infection from the vaccine itself. The AVEU addresses this concern in literature and videos shown to volunteers as part of the screening process. There is no possibility of contracting HIV from these vaccinations.
 Once screened by sexual history, volunteers undergo a physical exam and HIV blood test. If all is normal, volunteers read and sign detailed consent forms which indicate that they understand the protocol and the time commitment involved. Pre-trial blood is taken and a vaccination is administered. It may be an injection or one of the new mucosal vaccines, which are taken orally, intra-nasally, or in a variety of other locations.

Blood is drawn on nearly every AVEU visitphoto by Domino
Participants are then asked to observe a variety of things, including their temperature and any changes at the vaccination location. Trials last between one and two years. Visits to the AVEU are closely spaced at first, with occasional booster vaccinations. As the trial progresses, the visits decrease in frequency. Such visits are brief, lasting only long enough for a blood draw and a chat with Billy, Catrena, or Peter. Some days are “vampire draws” with several tubes of blood drawn, others are less draining and only a few tubes are taken. A small monetary compensation, between $25 and $50 for each visit is offered to study participants.
 Many potential volunteers have contacted the AVEU, but are concerned that they will test HIV positive after vaccination. The staff has trained extensively to address this concern and can provide documentation that a volunteer has no actual HIV in their body. Billy Tingle says, “I tell all my volunteers - don’t get tested anywhere else. If there is any question, if you messed up, I’ll test you. If the issue comes up with your job, your insurance, or whatever, don’t even get in the conversation, just call me. Usually, the phone rings and it’s handled. I know what information to provide and what to say. For example: Our tests do show at this volunteers’ last visit that he/she definitely was not infected.”

Visit the UABs 1917 AIDS clinic:

Care Team Network
Catrena Johnson has prepared letters describing the vaccine trials for insurance companies, the Army reserve, and several others. In no way should participation jeopardize a volunteer’s chances for employment or insurance. Volunteers are issued a photo ID card in case of an emergency, with a toll free number for clarification of any situation.
 It was interesting to find that Dr. Mulligan and many of his staff are volunteers participating in the vaccine trial. When asked why they’ve chosen to volunteer, they feel it would be wrong to ask anyone to agree to something that they wouldn’t want to be a part of themselves. Nurse Tingle believes “none of what we are trying is dangerous,” and adds “I question everything we do; I would never sit here and talk about participation if I think it’s gonna hurt them. My friends are in this. I’m in it. If someone calls and they are uneasy - we never push anyone. If there is any doubt, walk off. There is never any commitment, you can walk away at any time once you are in.” 
 Other reasons for participating are personal. Catrena Johnson, an African-American woman, says she volunteered because of her daughters. She hopes for a world where they have no fear of AIDS. With HIV currently the number one killer of African American women between 25 and 40, her concerns for the future are justified. She is also an advocate for female volunteers. “For heterosexual women, the prime group being infected now, they’ve got to realize that there’s not been a whole lot of research on women (and AIDS).” Says Nurse Johnson, “So we need to get into trial studies, not only for vaccines but all trial studies. We need to be represented, be it white, Asian, African-American, or whatever. I think it’s important for women to empower themselves and get involved. If we come up with a vaccine, everyone needs to be represented.” Both Billy and Catrena make it very clear that the AVEU is recruiting people, and not representatives of any particular community.
Billy Tingle’s reasons for participating are also personal “For myself - I’ve lost every classmate I went to college with, and I’m 36. So my whole group of friends disappeared. It was the only thing I knew to do, to get involved. Maybe the next group of folks who go through college can sit on the porch and get old together. I’m not going to have that.”

Katrena enjoyed this a bit more than I did, photo by Domino
Everyone at the AVEU is involved in recruiting. Whether it’s Dr. Mulligan seeing patients, partners, friends and families in the clinic, Catrena at a local cultural festival, or Billy at a table during Gay Pride, the AVEU is constantly seeking new volunteers. Nurse Peter Bonventre has recently joined the AVEU staff as a recruiter as well.
 The goal of the AVEU is not to hit a home run and develop the perfect vaccine. The AVEU researchers hope to test and prove a vaccine with some level of “efficacy” or prevention. A vaccine 50% effective would still make a huge difference, especially in the developing world, where diagnosis and treatment of AIDS is problematical and impossibly costly. In the developing world, Dr. Mulligan says “The resources available are miniscule, and there are many problems that actually have urgency greater than AIDS; TB (Tuberculosis), Malaria, poverty, hunger, are killing people. AIDS is there, as this ever-present background, but they don’t even test for it - there is no money for testing. Young people get sick and die, and it’s just assumed that they have AIDS.”

Dr. Mulligan is resolute, he believes “We are a wealthy nation and it falls back to us to lead the way in AIDS development. Here at UAB, we are one of six centers in the country funded by the NIH as a human trial site for prevention vaccines. We have a unique position, in the country, really in the whole world in trying to develop these vaccines.”
 Like the development of AIDS treatments, the AVEU hopes for any change at first. Just as AZT offered some early relief and today’s protease inhibitors give increased quality of life, the first AIDS vaccine will not be a “magic bullet.” It will be the first of many bricks in the wall, which protects from infection.
 The AVEU is currently enrolling for many clinical trials, both Phase I and Phase II. People at lower risk for HIV are encouraged to call either Peter Bonventre at 975-2839 or Catrena Johnson at 975-2842. As defined by the CDC, lower risk is a person who practices safe sex and has fewer than four partners in a six month period. Women and minorities are encouraged to enroll, in the interest of keeping the trial representative.

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 Tod Companion is a Ph.D. candidate at the University of Alabama at Birmingham in the Department of Biochemistry and Molecular Genetics. The text of this article and other columns can be found at www.geocities.com/~todc. He can be reached by email at todc@geocities.com.

Even as a scientist, I remained skeptical of these trials. I spent a lot of time reading and researching the various vaccine trials. I knew they were safe, but I worried about many issues. I was concerned about testing positive with no HIV in my blood, a concern quickly eliminated by the staff. I thought I might wait until later phases of the trial. Many conversations made it clear to me that everyone contributes equally, from the control volunteers who get no vaccine, to the last injection of a revolutionary new vaccine. You have to walk before you can run.
In the end, it was my desire to contribute to the fight against AIDS that led me to volunteer. Like Billy, I saw an entire generation of men struck down in their prime. I have marched, protested, cared for the ailing and delivered meals; but this trial was a tangible contribution to the fight against AIDS. My protocol ends soon, and I must admit I’m sad that I won’t see my friends Billy and Catrena as often. But I take pride in the fact that I’ve made a difference, I rolled up my sleeve, and I hope you will too.

Tod