By James Ricci
http://www.latimes.com/news/local/la-me-elites6jul06,0,7217065.story
http://tinyurl.com/kqz5z

Los Angeles Times
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California | Local News

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HIV-Positive Group May Hold the Key to Defeating AIDS

  Infected but not ill, 'elite controllers' make up less
  than 1% of those with the virus. They may hold the key
  to its cure.

  By James Ricci, Times Staff Writer
  July 6, 2006
  SAN FRANCISCO -- Matt Traywick's personal life has been
  a treatise on how to contract AIDS.

  A gay man, he'd been "very sexually active" in San
  Francisco in the late 1970s, he said, and tended toward
  unprotected encounters. Then he entered a long-term
  monogamous relationship, and after he lost both it and
  his job as a computer specialist, he sank into a life
  of hard revelry and so much intravenous methamphetamine
  use that he wound up homeless on the streets of the
  city's Tenderloin district.

  "I always knew I would be HIV-positive," Traywick
  recalled. "I hit all the major risk factors. It seemed
  there was no way I would have been negative. When I
  tested positive, my doctor cried and I didn't. Walking
  home, I wondered if there was something psychologically
  broken in me because, for some reason, I wasn't
  worried."

  Against all logic and expectation, his nonchalance has
  turned out to be justified.

  Traywick was diagnosed 21 years ago and has been
  healthy ever since, despite never having taken anti-HIV
  medications. Antibody tests demonstrate conclusively
  that he harbors the virus. But his immune system has
  controlled it so effectively that repeated blood assays
  have never shown a detectable level of the invader,
  even though Traywick still occasionally uses speed and
  engages in unprotected sex.

  A graying, rumpled man of 46 with darting eyes and
  nervous hands, Traywick said he has "spent a lot of
  time trying to figure out why I was a survivor. There's
  got to be a reason some people are chosen not to die."

  In the argot of AIDS research, Traywick is an "elite
  controller." Elites are extremely rare, accounting for
  an estimated one-third of 1% of known HIV-positive
  people and numbering perhaps 2,000. They and so-called
  viremic controllers, healthy infected people whose
  immune systems keep the virus at very low, although
  detectable, levels in the blood without drugs, are of
  keen interest to AIDS researchers.

  "I would say we still don't have the faintest idea why
  these people are doing as well as they are," said
  Harvard medical professor Bruce Walker, director of the
  Partners AIDS Research Center at Massachusetts General
  Hospital. "Achieving the state that these guys have
  reached in their bodies -- if we could do that through
  some intervention, we would solve the AIDS epidemic."

  Being a long-term controller is not an unalloyed
  blessing, as Kai Brothers' journey illustrates.

  Brothers, 43, a computer technician for Wells Fargo
  bank in San Francisco, got his first indication
  something was amiss in 1987. A frequent blood donor, he
  received a certified letter from his blood bank stating
  that someone had donated HIV-tainted blood and asking
  him to be tested.

  Brothers couldn't bring himself to respond. As a gay
  man, he knew he was in a high-risk group. Eventually he
  had himself tested but couldn't face learning the
  results. It was 1989 before he had himself retested,
  confirming his suspicions.

  "I deep-down knew," he said in a recent interview.
  "There was a heavy feeling but not a surprise or shock.
  There was fear: 'Am I getting sick? How long will it
  take before this time bomb went off?' "

  Not knowing his future, he quit his job and cashed in
  his 401(k) account to travel in Europe. On his return,
  he learned his infection-fighting T-cells -- HIV's
  target -- had dipped slightly below the normal range,
  and his doctor wrote him a prescription for AZT, the
  first effective HIV drug but one with often dreadful
  side effects.

  "I decided I was not going to get it filled," Brothers
  recalled. "Something instinctively told me not to. I
  decided to wait it out."

  Wait he did, and although his T-cells occasionally
  dipped, he also declined to use the effective
  multi-drug HIV cocktail when it became available in
  1996. A man of moderate habits, Brothers took to
  practicing safe sex -- although researchers think it
  unlikely that controllers can infect others, he has
  taken no chances -- and listening more closely to his
  body when it requested food or rest or exercise.

  While the AIDS epidemic roared through San Francisco's
  gay community, killing his partner and several close
  friends, Brothers escaped unharmed.

  "But it was a bittersweet feeling," he said. "It's hard
  to call yourself a survivor when you've been through so
  much devastation, so profoundly affected by loss and
  grief. Isolated was definitely something I felt at the
  end of the '90s. I used to go to support groups and
  hear what everybody else was dealing with, having AIDS
  and opportunistic infections. It was uncomfortable
  because a lot of them were upset or angry or
  frustrated. I couldn't identify with them, and I
  couldn't identify with those who were HIV-negative."

  Such feelings of isolation are common among
  controllers, said Dr. Florencia Pereyra of the Partners
  AIDS Research Center. She established a small support
  group for controllers in Boston and found that "because
  they're not on medication and don't have high mortality
  rates, they feel apart from the rest of the HIV
  community."

  Another common sentiment among them was a desire to be
  studied. "The question seems to come back to them all
  the time," said Pereyra: "Why me? What's so special
  about me?"

  To divine the answer, researchers are, among other
  efforts, probing the body's so-called innate immune
  system, trying to discern if controllers harbor a
  defective form of the virus and undertaking an
  unprecedented study of hundreds of controllers in an
  attempt to learn if there is anything genetically
  unique about them.

  Enigma
  (Robert Durell / LAT)
  June 22, 2006
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  Healthy
  (Robert Durell / LAT)
  June 22, 2006
  [clicktoenlarge.gif] click to enlarge
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  Medicine
  (Vadim Ghirda / AP)
  May 25, 2006
  [clicktoenlarge.gif] click to enlarge
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http://tinyurl.com/ev82w

  Human beings have two immune systems, the innate and
  the adaptive. The innate system is a general response
  to any incoming pathogen, and it can kick in almost
  immediately. Its component cells, including some known
  as "natural killer cells," dismantle viruses, kill off
  early cancer cells and engulf and eliminate foreign
  bacteria.

  The adaptive system, which is dependent largely on
  infection-fighting T-cells and antiviral antibodies, is
  more finely tuned and needs to identify an invader
  precisely before going into action, a process that
  takes days or weeks. Thus far, the great bulk of HIV
  research has centered on the adaptive system.

  Researchers at UC San Francisco have assembled a group
  of 50 elite controllers (including Traywick), and
  research on them has produced an intriguing discovery.

  About half of the elites control the virus, as
  expected, through a powerful response by T-cells.

  The other half shows no such T-cell response.

  "The 25 people in our cohort who have no T-cell
  reaction can provide insight into whole new ways of
  thinking," says Dr. Steven Deeks, a prominent HIV
  researcher at UC San Francisco. "There are 25 guys who
  have no reason for controlling the virus."

  Because their adaptive immune systems appear to play
  little or no part in controlling the virus, they are
  prime subjects for investigation into the innate immune
  system.

  Since 1984, Dr. Jay Levy, director of the Laboratory
  for Tumor and AIDS Virus Research at UC San Francisco
  and one of the first to isolate HIV, has focused on the
  innate immune system and its unique infection-fighting
  tools.

  In all of the controllers he has tested, Levy found
  evidence of an effective antiviral protein secreted by
  certain innate immune system cells. Over the last two
  decades, he and his team have searched through the
  thousands of proteins these cells make in the hope of
  identifying the antiviral protein. They've managed to
  narrow the number to about 80, but they need to winnow
  it further.

  They've also been trying to identify the gene that
  causes controllers' cells to express the antiviral
  protein. Of the body's 37,000 genes, Levy's team
  identified, through several experiments, eight that
  look promising; they expect to identify five or six
  more.

  Eventually, they'll introduce the most promising genes
  into human cells and look for the antiviral protein
  activity.

  Levy is also looking at another tool of the innate
  immune system, a small number of cells that produce
  virus-crippling interferon. He has found that
  controllers have higher numbers of these cells than
  even healthy HIV-negative people.

  Essentially, controllers show that the human immune
  system is capable of containing HIV naturally, Levy
  said. "This has been a long time coming, but in my
  opinion we can look forward to long-term survival
  without toxic drugs."

  Some researchers have theorized that controllers are
  able to contain the virus because the strain of the
  virus they're infected with is somehow defective.
  Although the current belief is that a defective form of
  the virus does not in itself explain controllers'
  success -- it might even be that the virus is capable
  of repairing itself -- researchers haven't been able to
  tease the virus out of some elite controllers so that
  it can be examined for defectiveness.

  "Whenever researchers find the virus, it usually looks
  normal," Deeks said. "But some of the people in whom it
  can't be found, it may be they were exposed to a
  defective virus."

  To examine every controller for defective virus would
  be prohibitively expensive, he said. If such a study
  were mounted, he said, the idea would be "to see if the
  virus is there and if it is defective, because in
  theory that virus will give good insights into making
  an effective vaccine."

  One of the problems with studying elites is that there
  are so few that researchers haven't been able to
  assemble local research cohorts large enough to study
  effectively. Now, however, Walker of Massachusetts
  General and his collaborators hope to collect blood
  samples from 500 to 1,000 elite controllers and a
  similar number of viremic controllers, subject them to
  detailed genetic analysis and compare the findings with
  those from two groups: HIV-negative people and
  HIV-positive people in whom the virus has progressed.

  Working through AIDS caregivers and AIDS advocacy
  groups, the Massachusetts General team has amassed 76
  elite controllers and 100 viremic controllers from
  across the country and is funding collaboration with UC
  San Francisco's cohort of 50 elites and 50 viremic
  controllers, including Brothers.

  "Basically, we want to recruit every single one of
  these people in the United States," Walker said. "We
  have to have a large enough sample to begin to see
  patterns in this population."

  He is optimistic that the genetic survey "will show
  exactly what the mechanisms are that will reveal drug
  targets that we can focus upon."

  While researchers pursue various avenues for explaining
  his uniqueness, Matt Traywick is trying to put his life
  back together.

  After his two years of homelessness, which included a
  brutal beating that hospitalized him for more than two
  months, he is living in Catholic Charities-supported
  housing, where he shares a bathroom with another tenant
  and visitors must leave identification at the front
  desk.

  He said he still uses methamphetamine "only every
  couple of months" and remains sexually active. "I don't
  always keep myself safe, but I'd never put someone else
  at risk," he said. "I always disclose. I've never been
  so high that I didn't remember or think to disclose."

  A potential irony of the highest order: Levy's research
  suggests that the protection provided elite controllers
  by the mystery antiviral protein fades in about a year
  after exposure to HIV, so that regular re-exposure
  might play a role in keeping a controller safe.

  In any case, Traywick recently posted a resume on the
  Internet and has drawn a few interested responses from
  potential employers.

  "For the first time in many years, it looks promising,"
  he said.

  He knows he's got to return to a productive life in
  order to save for retirement.

  "I didn't think I'd make it to 30, much less 46," he
  said. "I never dreamed I'd retire. Now it looks like I
  might. That's the ultimate joke that God plays on us
  guys."

http://www.latimes.com/news/local/la-me-elites6jul06,0,7217065.story
http://tinyurl.com/kqz5z
By James Ricci