Merck’s Experimental AIDS Vaccine Demonstrates Promise in Early Human TrialsMerck & Co.'s experimental AIDS vaccine, seen by many AIDS experts as the "best chance" for slowing the spread of the epidemic, has elicited a strong immune response in preliminary human safety trials, according to study results presented yesterday at the Ninth Conference on Retroviruses and Opportunistic Infections, the Newark Star-Ledger reports. "It's encouraging. This is the first time this type of vaccine has been used in humans, and the immune response we're seeing is comparable to what we observed in monkey trials," John Shiver, Merck's head of vaccine research, said (Silverman, Newark Star-Ledger, 2/27). The vaccine, which does not seek to prevent HIV infection but aims to elicit an immune response to keep the virus in check, uses a disarmed cold virus, or adenovirus, to deliver HIV DNA into blood cells, where it "alert[s]" the immune system to its presence, prompting a "killer" T cell response (Sternberg, USA Today, 2/27). The adenovirus is re-engineered so it will not cause infection, and the HIV DNA "poses no apparent health or safety risk" on its own. According to Merck, about half of the study participants who received "various doses" of the vaccine "showed positive T cell responses." Shiver noted that the increased response may be due to the fact that most Americans have at some point in their lives been exposed to the adenovirus and have already developed antibodies to the virus (Pierson, Reuters, 2/26).
The Common Cold
Researchers worried that because the base virus was so common, the immune system may attack the vaccine before it could deliver the HIV DNA. To compensate, researchers tested subjects for adenovirus antibodies before administering the vaccine and gave those who tested positive higher doses of the vaccine. In 57% of participants with pre-existing antibodies to the adenovirus, the vaccine "appeared to overcome" the antibodies and produced an immune response to HIV. Merck hopes to use the adenovirus vaccine in tandem with "naked DNA" -- a shot of disabled HIV DNA -- to elicit an even greater immune response. This approach proved successful in monkeys, and researchers think that the two-pronged approach could "help overcome the pre-existing [adenovirus] antibodies." Merck also plans to add more HIV genes to the vaccine to make it more effective for a greater number of people. The adenovirus vaccine and the "naked DNA" shot were tested separately in humans until the vaccines' safety was verified. So far, the only complaint about the adenovirus vaccine is that at its highest dose it causes "moderate and sporadic malaise and body aches" (Schoofs, Wall Street Journal, 2/27). Merck researchers began injecting test subjects with both components in December, but it is too soon to draw conclusions from those results (USA Today, 2/27). Merck plans to test the vaccine in about 600 volunteers. About 150 volunteers have been enrolled so far at 60 sites in the United States. Emilio Emini, head of Merck's AIDS vaccine initiative, said that if all goes well, it will be "at least five years and probably longer" before the vaccine would come to market (Haney, AP/Owensboro Messenger-Inquirer, 2/27).
Dr. Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases, which will work with Merck to conduct the human safety trials, said yesterday that the vaccine elicited "the best immunological responses I have seen." However, he cautioned against comparing vaccine studies (Wall Street Journal, 2/27). Dr. David Gold, vice president of the International AIDS Vaccine Initiative, called the results "significant," but said "there are still a lot of details that need to be fleshed out." Merck's "willingness to invest" in the vaccine "shows they have tremendous confidence they are on to something," Lee Klosinski of AIDS Project Los Angeles said (Maugh, Los Angeles Times, 2/27). Merck has recently "invest[ed] heavily" in AIDS research after it "t[ook] a beating" for going to court with developing nations over AIDS drug patents, the Star-Ledger reports (Newark Star-Ledger, 2/27).
Several other studies reported at the conference have appeared in the media. The following is a summary of some of those studies:
- Researchers from the 25-nation EuroSIDA study yesterday said that people with HIV who delay starting or who interrupt treatment "may face substantial hazards," the Washington Post reports. The study followed 5,400 HIV-positive individuals with "relatively advanced infections" over five years and found that those who ceased taking antiretroviral medications for "at least three months" had six times the risk of dying or developing serious AIDS-related complications. Those who resumed taking their medications -- as most did -- still had nearly twice the risk of death as those who maintained a faithful drug regimen. The phenomena was seen only in people with CD4+ T cell counts below 200 cells per milliliter of blood. Normal CD4+ cell counts are above 800. Most of the 20% of participants who stopped taking medication at some point did so because the drugs "were not fully quelling virus growth."
- Researchers from the University of Washington found that beginning treatment early, contrary to popular practice, may be more beneficial than waiting until CD4+ cell counts fall. Current federal treatment guidelines recommend waiting to begin treatment until CD4+ cell counts fall below 350. The study followed patients who enrolled for treatment at the university clinic and found that those who began treatment within the first year of enrollment had less than half the risk of death or serious complication compared to those who waited more than a year to begin drug therapy.
- Researchers from Johns Hopkins University found that antiretroviral treatment may be "especially important" for people over the age of 50. Researchers compared the results of about 250 older HIV patients with those of about 550 patients under the age of 50 and found that older people who elected not to take antiretroviral drugs had twice the mortality of younger people who also forwent treatment. However, people over the age of 50 who elected to take AIDS drugs responded just as well as younger people (Brown, Washington Post, 2/27).
- Offering widespread access to post-exposure prophylactic AIDS drugs does not promote a "quick fix" mentality that leads to a rise in risky sexual behavior, according to a study from the Universidade Federal do Rio de Janiero in Brazil presented Monday, MSNBC.com reports. Brazilian researchers offered the AIDS drugs ZDV and 3TC, which are "routinely" given to health care workers who may have been exposed to HIV in the line of duty, to 200 gay men. All of the men were given a four-day supply of the drugs at the outset of the study and told to take two pills a day and to contact the clinic if they engaged in any risky sexual behaviors. At the clinic, their risk level was evaluated, and those deemed to be at risk -- those who engaged in unprotected anal, vaginal or oral sex -- were given a 24-day supply of the drugs to complete the 28-day regimen. PEP was used 110 times by 73 men over the course of the two-year study. The full drug course was finished 91% of the time compared to a 50% to 70% completion rate among health care workers. Eleven cases of HIV infection occurred -- 10 in men who did not use PEP and one in a man who used the drugs but was exposed to a drug-resistant strain of the virus. Participants actually recorded a decrease in risky sexual behavior over the course of the study, with 57% reporting that they engaged in some type of unprotected sex at the outset compared to 40% at the completion of the study. "This study shows you can educate people so that they don't use [PEP] as a substitute for safe sex practices," Dr. Mauro Schechter said, noting that the men also received one-on-one counseling about HIV prevention at the clinic (Sommerfeld, MSNBC.com, 2/25).
- Using genetic "fingerprinting" technology, researchers from China and New York said Monday they have determined that China is "suffering from distinct epidemics" of both HIV and hepatitis C, the Wall Street Journal reports. Linqi Zhang of the Aaron Diamond AIDS Research Center, which has helped coordinate AIDS treatment clinical trials in China, presented the study, which found that infected individuals in the southern province of Yunnan had HIV subtype C while people in central Henan province had subtype B. The study also determined that hepatitis C in Yunnan -- where both diseases are spread largely through intravenous drug use -- is "dominated" by the subtype 3 strain of the virus, while subtypes 1 and 2 were found in Henan -- where HIV and HCV were mostly spread due to unsafe blood collecting practices. Dr. Yunzhen Cao said the government has recently permitted a few pilot needle-exchange projects to be set up in Yunnan, which is mostly inhabited by ethnic minorities, and has "cracked down" on illegal blood centers throughout the country.
- Douglas Richman of the University of California said on Monday that HIV has a "startling ability" to rapidly mutate its outer envelope, presenting a problem for vaccine developers hoping to elicit an antibody response against the virus. "We see in six months in one patient what happens to the influenza virus around the globe in a decade," Richman said. However, the finding does not mean that researchers should give up hope of defeating the virus. In fact, the rapid mutations mean that antibodies are placing "incredibly strong selective pressure" on HIV, "forcing" it to mutate to stay one step ahead of the body's immune system. Richman added that if a vaccine could elicit a strong antibody response "before the virus got a foothold inside the body," it may be able to ward off infection (Schoofs, Wall Street Journal, 2/26).