Newsday - Wednesday, July 10, 2002
Laurie Garrett, Staff Correspondent

Harvard Medical School's Dr. Bruce Walker startled scientists with word of an unusual patient who, despite building up an immune response to HIV, then acquired a second HIV infection from a closely related virus and suffered a major setback.

Scientists could be heard cursing and gasping as Walker presented his data, and noted French researcher Dr. Brigitte Autran leapt to the microphone following the presentation and exclaimed, "Bruce, it's terrible news!"

Walker has for several years been trying to figure out how to trick the human immune system into fighting off HIV. Three years ago he showed that in the first days following infection most people make strong cellular immune responses against the virus. That response is called CTL, after the cytotoxic T cell lymphocytes involved in fighting the virus.

Walker's discoveries led many vaccine researchers, as well as Merck & Co., the drug-maker, to rev up efforts to develop vaccines that would fight off HIV using CTL.

The CTL findings also prompted Walker to try treating patients with anti-HIV drugs immediately after infection for a few weeks, then taking them off the medicine to allow their immune systems a chance to detect the viruses as they surged out of hiding. Many dreamed two years ago that this approach could constitute a sort of therapeutic vaccine.

Walker has 14 patients undergoing that therapeutic approach for more than two years. His disturbing address today focused on one of those patients, a gay man from Boston.

The man went through two rounds of on/off medication and seemed to be doing extraordinarily well.

"But then something changed," Walker said. In one month's time the viruses surged, and when genetically analyzed they proved to be 12 percent different from the type of HIV in the patient just 30 days earlier. The patient's immune system was suddenly helpless in the face of this apparently new HIV.

The patient said he had recently had unprotected sex with a male partner. The man was superinfected with another virus, 88 percent identical to the first.

"He never got a new response against the second virus, and he declined clinically," Walker told the stunned audience. "The public health implication of this is that it is possible to become infected with a second strain of HIV, even a very closely related one."

There have been a few prior, albeit controversial, reports of superinfection, involving individuals who were exposed to two highly different forms of HIV. For that reason, vaccine researchers have assumed that an effective protective vaccine would have to be made up of samples of each of the major seven or eight classes of the virus now circulating around the world. But Walker's patient was infected with two viruses from the same class, genetically very similar.

To put this into perspective, a measles vaccine containing elements from just one type of measles virus protects against infection with all forms of the virus, worldwide. AIDS researchers had already been worried about the difficulties involved in making a complicated vaccine with seven or eight viral samples. The implications of Walker's discovery could be that a protective vaccine -- at least in terms of raising cellular immune responses û would have to contain hundreds, maybe thousands of viral samples. Such a massive vaccine would be impossible to test and manufacture, and may not be tolerable to human beings.

"This case, albeit anecdotal, has shattering implications for the development of a prophylactic vaccine," Cornell University AIDS vaccine researcher John Moore lamented. "The strength of the cellular immune response at the time of exposure was substantially greater than you get from vaccination, but it could not prevent infection. That's a big problem!"

Dr. Wayne Koff, who heads up research for the International AIDS Vaccine Initiative, a private effort based in New York, shared concerns that, "if you really can be infected, control the infection, come back and be reinfected with a similar virus û it has serious implications for vaccines."

Merck has invested heavily in development of a vaccine that is designed to raise CTL reponses, and be used therapeutically by people who are already infected. Dr. Emilio Emini, who heads up that effort, described the Walker findings as puzzling and dismissed the case as a rarity.

But Dr. Margaret Johnston, who heads up the National Institutes of Health's AIDS vaccine program, noted that nobody really knows how common superinfection may be.
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