Baylor College of Medicine seeks study volunteers
by Rich Arenschieldt
The 20-year search for a vaccine to combat HIV has been a “one step forward, three steps back” process. The now-famous 1984 quote by U.S. Secretary of Health Margaret Heckler, that “there would be a vaccine expected for testing in two years,” has seemingly jinxed a complicated, expensive, and incremental process. Dr. Hana El Sahly, a physician and assistant professor in the Department of Molecular Virology and Microbiology at Baylor College of Medicine, has thrown her stethoscope into the ring to help solve one of the this era’s major health challenges—discovering a disease-modifying or preventative HIV vaccine.
“Looking for vaccines to tackle HIV has been on the agenda since the identification of the virus,” El Sahly says. Enormous human and monetary resources have been dedicated to previous trials, most notably, the AIDSVAX trial which ended with a whimper in 2003, and the more recent STEP trial which also showed no benefit. A glimmer of hope emerged from the 2009 “Thai” trial. Of the 16,000 volunteers who participated, some who received the vaccine evidenced a modest benefit in the prevention of HIV transmission.
The trial that Baylor is currently enrolling, “HVTN 505,” will utilize lessons learned (and errors corrected) from previous endeavors—now standard practice in designing and implementing new trials. “Each time a trial concludes, its results are dissected and made public,” says El Sahly. “Statisticians mine the data for information so that the design and strategy of the next clinical trial is informed by its predecessor—especially with regard to patient safety and maximization of clinical benefit.”
This HVTN 505 trial was started over a year ago with the goal of evaluating two “endpoints” or significant events. First, how many participants become HIV infected? Second, in those who become infected, does the vaccine reduce HIV viral load (amount of HIV in the bloodstream) compared to those who receive a placebo? With these two goals, this study possesses both preventative and therapeutic components.
“We improved the design of this trial in order to achieve better outcomes,” El Sahly says. “Also, we are using a remarkably different vaccine ‘platform’ than previous trials, utilizing a ‘broader’ vaccine [one that has efficacy against more strains of HIV], as well.
“We also have taken additional safety steps to screen out individuals who, in previous trials, were at increased risk for acquiring
HIV—specifically, men who are uncircumcised and those who carry a certain type of ‘Adenovirus’ [a virus that causes the common cold].”
This trial uses what is known as a “prime-boost” strategy, one that seeks to boost the body’s immune response at different times in slightly different ways. “This involves administering three ‘prime’ doses of vaccine to illicit a limited initial response, and then a subsequent ‘booster’ dose that causes more direct immune activation,” El Sahly says. “Based on the preparation work that has been done in preclinical trials for this vaccine, this approach appears likely to be the most successful.”
This dual approach “presents” the immune system with a harmless, genetically constructed HIV-like “Trojan horse” in two slightly different forms. The goal is to trick the immune system into responding to each antigen separately and to mount a dual defense against infection in addition to lowering an individual’s HIV viral load.
While this all seems daunting to potential study volunteers, it’s important to be reminded of some things we already know: first, vaccines are given all the time, and the same goals that apply to measles and mumps apply here—prevention or mitigation of disease without harm to the patient; second, vaccines don’t give you disease, which is especially important in this case.
“For this trial, we seek to enroll 1,350 volunteer participants nationally,” El Sahly says. “Here at Baylor we have been enrolling since November and are actively recruiting, hoping to enroll between 50 and 100 volunteers locally.
“We seek healthy, sexually active men who have sex with men—homosexual, bisexual, or male-to-female transgendered individuals,” El Sahly continues. “They must be HIV negative, circumcised, and have had at least one or two sexual partners in the last six months. This is a randomized, double-blinded study, i.e., the participants may receive the vaccine or a placebo.”
There are some risks associated with enrolling in any clinical trial, and these will be carefully discussed with each potential participant as part of the “informed consent” process, when patients and clinicians outline their respective roles and responsibilities.
“Volunteers will know from the onset that their safety is foremost in our minds during the trial,” says El Sahly. “The study will be continuously overseen by an independent safety monitoring board. This entity assures that no participant is subject to any undue harm. Also, any information that the volunteer shares with us regarding their specific sexual behavior, lifestyle, or sexual partners is completely confidential. A discussion of ‘risk reduction’ strategies to prevent HIV infection will be included in the screening appointment and in every subsequent visit with us.”
Interested volunteers will have an initial screening over the phone, and then meet with medical staff in person to review the study consent forms and answer any questions. A routine medical exam, including blood tests, will be done to determine eligibility. Upon successful completion of those tests, the volunteer will be enrolled. At that point participants will be “randomized” into either the vaccine group or the placebo group. Researchers will then see the volunteers every month for three months and in three-month intervals after that for three years. Volunteers will receive compensation for each completed visit.
While this vaccine will not give you HIV, it can result in what El Sahly calls “vaccine-induced antibody positivity.” This means that some volunteers receiving the vaccine may develop HIV-specific antibodies without actually being HIV-infected.
Obviously, this has the potential to cause complications among medical providers, employers, and insurers—something El Sahly and her colleagues are keenly aware of. “Some people ‘lose’ these vaccine-induced antibodies over time, but we do ask that volunteers get their subsequent HIV testing with us at Baylor. Even if the study concludes and participants relocate, we will give them a toll-free phone number to call for free testing, and we will send the results to them or their doctor.” This specialized testing will provide proof that volunteers are not HIV-positive in spite of the presence of certain antibodies.
As the result of the “Thai” trial and some very recent advances in HIV research, Dr. Sahly, like many of her colleagues, is optimistic about what can be gleaned from the HVTN 505 trial. “We hope that the work clinicians and volunteers accomplish together in the months ahead results in substantial progress towards the development of a vaccine that prevents HIV infection,” she says.
Volunteers who enroll may not win a Nobel Prize, but the creation of every successful vaccine in history resulted from the efforts of courageous, forward-thinking individuals who sought to make more than an incremental impact in their world.
For more information, e-mail [email protected] or call 713/798-4912.
Rich Arenschieldt is a frequent contributor to OutSmart magazine.
Comments