LifeGuide [Treatment Horizons]

 

With HIV treatment studies well-covered in the New York City area, “the mission of Project ACHIEVE has been focused on developing and testing ways to prevent HIV infection,” says Dr. Beryl Koblin, Project ACHIEVE’s principal investigator and head of the Laboratory of Infectious Disease Prevention of the New York Blood Center, as well as an adjunct faculty member at the Columbia University School of Public Health, the Project’s partner in conducting HIV research.

The organization’s prevention studies—all of which are nurtured by a community advisory board—include behavioral interventions, almost exclusively focusing on those not HIV-positive. (A recent exception is Project MIX, a study to see whether a group behavioral intervention for HIV-positive and negative men who have sex with men can reduce sexual risk while under the influence of alcohol and other drugs.) Developing behavioral prevention strategies is only part of the Project’s work: conducting preventive vaccine trials is another essential component.

Project ACHIEVE is currently enrolling for several Phase I trials, among them HVTN 044 and the newly launched Merck trial 023. HVTN 044 will primarily gather information about the safety of the vaccine in humans and dosing amounts, as well as measure the immune response. According to Dr. Koblin, the 044 vaccine candidate exemplifies the direction vaccine reasearch has increasingly taken: “promoting the cellular arm of the immune system as a means to prevent HIV infection.” HVTN 044 is a DNA plasmid vaccine, combined with an adjuvant (a substance to help the body respond to the vaccine). This vaccine uses a synthetic plasmid to house and deliver synthetic HIV genes into cells; these genes carry instructions for making the proteins Gag, Pol, and Nef from subtype B HIV-1, among others. These proteins, similar to the ones that HIV produces, are expected to teach the body how to defend itself against HIV.

The Merck 023 trial will test the concept that the vaccine prevents HIV infection, or results in lower HIV levels in those who become HIV-positive. The Merck candidate focuses on the delivery of these same three synthetic genes, theoretically generating immune responses against subtype B HIV-1 by producing T cells and killing HIV-infected cells. This vaccine uses a weakened adenovirus as a delivery vehicle. Adenoviruses are among the main causes of upper respiratory tract ailments, but the one used has been modified so that trial participants won’t develop an infection.

Readers should be reminded that experimental vaccines used in all phases of testing are not produced from live virus or from HIV-infected human cells. You can’t become infected by HIV by participating in these trials. With experimental vaccines, however, researchers sometimes are not yet aware of all the potentially harmful effects they can have in humans. But Project ACHIEVE diligently alerts trial candidates of this fact as well as the risks they do know about. “It’s our first priority—to monitor safety,” says Dr. Koblin.

She mentions other risks beyond the physical. If a person is tested for HIV outside of the study, for example, a participant may receive an HIV-positive test result because the vaccine has made HIV antibodies. The appearance of being HIV-positive might cause problems if one is applying to the military or for long-term health or disability insurance. Says Dr. Koblin: “There are ways to tell if someone is reactive to the vaccine versus whether they’ve become infected: ELISA tests, specific to a couple of proteins which would be present in someone who is infected but not in someone receiving the vaccine, as well as PCR [polymerase chain reaction] tests are available.”

Project ACHIEVE also educates trial candidates about its rationale for conducting the trial, breaking down each step of the trials-long process toward (the as-of-yet far-off) licensing, demystifying how the vaccine potentially works, and explaining their part in the research. The Project’s staff will answer any question a candidate might have. This is where educating the general public about vaccines can help. Project ACHIEVE works with community-based organizations and colleges, distributes educational materials, and hopes to launch a television spot this year. This education is needed to marshall support and also recruit more volunteers, which perhaps now are needed more than ever. In the last five years, says Dr. Koblin, “there have been a lot more ideas and candidates out there, which I think is exciting. We know a lot more about the virus. The fact that we have so many protocols going on is a positive sign because the vaccine pipeline is a lot fuller.”

Contact Project ACHIEVE at (212) 388-0008 or log on to www.projectachieve.org for more information. Those interested may also call 1 (877) NYC-HVTU or log on to www.nychvtu.org.

Chael Needle wrote about computerized health stations in the January issue.

February 2005