Researchers Report Merck AIDS Vaccine May Not Provide ‘Total Protection’ Against Disease Progression

Researchers from Boston's Beth Israel Deaconess Medical Center yesterday announced that an initially "promising" vaccine for HIV developed by Merck & Co. may not provide "total protection" from the virus, the Long Island Newsday reports. Three out of four monkeys who were vaccinated got sick and died during the three-year follow-up period of the vaccine trial, researchers reported at the 10th Conference on Retroviruses and Opportunistic Infections in Boston. The vaccine uses a two-step "prime" and "boost" approach in which volunteers receive two injections of HIV genes. The "prime" vaccine contains HIV genetic material that aims to stimulate the body to produce viral proteins. The second "boost" vaccine contains additional HIV genes carried into the body by a "hollowed-out" virus, according to the Newsday. Together, the injections are designed to prompt the body to produce cytotoxic T-lymphocyte cells, or "killer T cells," which can kill HIV-infected cells. While researchers recognize that this approach may not prevent HIV infection, it may be able to keep levels of the virus low, preventing progression to AIDS. Dr. David Ho, scientific director of the Aaron Diamond AIDS Research Center, called the death of the monkeys "enough to be worrisome," adding that the vaccine field has been considering a shift back to an older strategy. The older tactic, previously thought to be "unworkable," seeks to stimulate the immune system to produce antibodies that would recognize HIV before it establishes an infection. While the body does make antibodies against HIV, the antibodies have not been able to penetrate the virus' surface. New studies, however, suggest that it is possible to produce antibodies that are able to penetrate the surface of the virus, and studies are under way to trigger the production of such antibodies in the body. Despite this recent shift, the majority of vaccines that have reached human trials are based on the prime-boost approach, including another vaccine by Merck that has been tested on 600 human volunteers. The Beth Israel researchers warned that conference attendees should not "read too much into" the death of the monkeys, noting that they had received only the prime part of the vaccine and that the prime-boost strategy when delivered to humans will be "more sophisticated," carrying more viral genes to prompt the body to produce antibodies. Although the current trial showed that the vaccine cannot completely stop the virus, the vaccinated monkeys fared much better than those that were not vaccinated, showing that the vaccine "has the ability to slow disease progression," according to Norman Letvin, one of the researchers (Haney, Long Island Newsday, 2/12).

HIV Vaccine Elusive?
Despite some notable successes, scientists at the conference "remained gloomy" about the prospects of finding a "universally effective" vaccine in the face of the rapid spread and mutation of HIV, which has at least nine different strains, the Boston Globe reports. While there are many vaccines currently being researched, only one has reached the third phase of clinical trials -- the last step before FDA approval (Smith, Boston Globe, 2/13). VaxGen's AIDSVAX, which utilizes a more "traditional" method of using the outer shell of HIV, has been given to 7,900 volunteers in the United States, Europe and Thailand. Results from the trials are expected within the next two months (Long Island Newsday, 2/12). The scientific community has greeted AIDSVAX with skepticism, pessimistic that the vaccine will be effective in a high percentage of recipients, according to the Globe. Researchers at the conference called for better collaboration among scientists and increased government and pharmaceutical company support for vaccine research, adding that they must continue to search for an effective vaccine (Boston Globe, 2/13).

Other Scientific Findings

• Structured treatment interruptions: Researchers at the conference yesterday debated the meaning of varied findings from studies of the effects of "structured treatment interruptions," or breaks in antiretroviral treatment, the Washington Post reports. Studies from Thailand, Spain and the United States suggest that open-ended treatment interruptions, which resume treatment when patients' CD4+ T cell counts or viral loads reach a specific cutoff, are more useful than shorter breaks, which some assumed to be safer. Treatment breaks are "appeal[ling]" as a means of making the expensive medication go further in resource-poor countries and because patients often forget to take medications or avoid taking pills to avoid immediate side effects. Researchers also agreed that frequent interruptions of antiretroviral therapy may promote the emergence of drug-resistant strains of the virus (Brown, Washington Post, 2/13).
  
• HIV transmission through breastmilk: A study conducted by researchers from Stanford University and the University of Zimbabwe found that HIV-positive women who were given a single dose of the antiretroviral drug nevirapine during labor develop and retain drug-resistant HIV strains in their breastmilk, Reuters Health reports. The small clinical trial, conducted in Chitungwiza, Zimbabwe, shows that using nevirapine to prevent mother-to-child HIV transmission during labor can result in an increased risk of later transmission of drug-resistant strains of the virus through breastmilk. The most common viral mutations conferred resistance to other non-nucleoside reverse transcriptase inhibitors, the class of drugs to which nevirapine belongs (Mitchell, Reuters Health, 2/12). Forty percent of women who took the drug showed drug-resistant strains in their bloodstream, while 65% had the strains in their breastmilk (Garrett, Long Island Newsday, 2/13). Dr. Constance Benson, a researcher at the University of Colorado Health Science Center who did not participate in the study, said that the findings should not cause AIDS workers to change their policies of administering the drug to HIV-positive pregnant women because the benefits still outweigh the risks (Reuters Health, 2/12).
  
• Vaccine tested on infants: The experimental ALVAC-HIV vCP205 vaccine, made by Aventis Pasteur, is safe in infants, according to the results of a Phase I/II trial, Reuters Health reports. The research, led by Elizabeth MacFarland of the University of Colorado Health Sciences Center, tested the prime-boost type vaccine on 23 infants born to HIV-positive women and found that the vaccine caused no serious side effects in the infants. Researchers hope to use vaccine as an alternative to drugs, which reduce the risk of mother-to-child HIV transmission through labor and delivery and breastfeeding (Fox, Reuters Health, 2/12).