Millions of gay men around the world are in mourning today as news of
two failed AIDS vaccines hit the news waves.
Bare-backers, homo-humpers, teeny-hiney-holers and all matter of anal
sex devotees had been anxiously awaiting the good news that they'd
soon be able to take a shot or some pills and never have to concern
themselves again with "safe-sex" and those inconvenient condoms and
other STD-preventive nostrums.
But erectile dreams and scalding visions of gang-bangy all-nighters
with untold numbers of unknown boys and men have been rudely quashed,
gone with the winds of reality.
So, go easy on those poppers, boys, and don't forget those rubbers,
dads, and try to locate anal virgins -- if there are any left --
rather than those greasy, uncut, stretched-anus, leather-and-bike
grunges that are sure to be HIV-positive.
Say, maybe it's time to go back to religion and the "church" to see if
your gayness can be "cured." Because there's nothing worse than being
horny and scared at the same time. Shoot a load and perish the
afterthought.
But many of you now will be ale to wen your butts off Depend diapers,
and gerbils can make a slow comeback from the endangered species list.
Anyway, it's back to the drawing board for that magic potion, which
many have predicted will NEVER successfully emerge from the test
tubes.
But there's always pickles, didos, and ballpoint pens, in a pinch.
------------------------
"Vaccine Failure Is Setback in AIDS Fight"
"Test Subjects May Have Been Put at Extra Risk Of Contracting HIV"
By David Brown
Washington Post Staff Writer
Friday, March 21, 2008; A01
The two-decade search for an AIDS vaccine is in crisis after two field
tests of the most promising contender not only did not protect people
from the virus but may actually have put them at increased risk of
becoming infected.
The results of the trials, which enrolled volunteers on four
continents, have spurred intense scientific inquiry and unprecedented
soul-searching as researchers try to make sense of what happened and
assess whether they should have seen it coming.
Both field tests were halted last September, and seven other trials of
similarly designed AIDS vaccines have either been stopped or put off
indefinitely. Some may be modified and others canceled outright.
Numerous experts are questioning both the scientific premises and the
overall strategy of the nearly $500 million in AIDS vaccine research
funded annually by the U.S. government.
"This is on the same level of catastrophe as the Challenger disaster"
that destroyed a NASA space shuttle, said Robert Gallo, co-discoverer
of the human immunodeficiency virus (HIV), which causes AIDS, and head
of the Institute for Human Virology in Baltimore.
The recently closed studies, STEP and Phambili, used the same vaccine
-- made from a common respiratory virus called adenovirus type 5 that
had been crippled and then loaded with fragments of HIV. Both studies
were halted when it became clear the STEP study was futile and
possibly harmful.
The results of the Phambili vaccine trial, which was conducted in
South Africa, were revealed last month and only worsened the gloom.
Although the number of new HIV infections in that study was far
smaller than in STEP -- and too few to draw firm conclusions from --
those results, too, hinted at a trend toward harm among vaccine
recipients.
Many researchers are questioning the scientific premises on which all
those studies were based and are wondering, along with AIDS activists,
what effect this near-worst-case scenario might have on tests of
future vaccines.
The working hypothesis for what went wrong is that the vaccine somehow
primed the immune system to be more susceptible to HIV infection -- a
scenario neither foreseen nor suggested by previous studies.
The National Institutes of Health, which funded the STEP and Phambili
trials, is convening a meeting next week to reassess its AIDS vaccine
program. But some respected scientists have already reached a verdict.
"None of the products currently in the pipeline has any reasonable
chance of being effective in field trials," Ronald C. Desrosiers, a
molecular geneticist at Harvard University, declared last month at an
AIDS conference in Boston. "We simply do not know at the present time
how to design a vaccine that will be effective against HIV."
He told a rapt audience that he has reluctantly concluded that the NIH
has "lost its way in the vaccine arena" and that he thinks it should
redirect its AIDS vaccine funds to basic research and away from human
trials.
In this fiscal year, the NIH's budget for AIDS vaccine research is
$497 million. The STEP and Phambili trials were each expected to cost
about $32 million. Pharmaceutical giant Merck & Co. has spent an
undisclosed amount developing the vaccine and helping to manage the
studies.
"We can't afford to have any more trials like this," said Mark
Harrington, head of the activist Treatment Action Group and a longtime
observer of AIDS research. "We have to stop and reassess and recommit
to basic science, or people will begin to lose faith."
At the moment, only two things are certain.
The first is that the vaccine, developed by Merck, could not have
caused HIV infection because it contains only three proteins from HIV,
not the entire virus. The second is that there are no obvious
villains.
"I do not think that what happened in this trial is an example of
scientists blindly rushing into dangerous things," said John P. Moore,
an AIDS virologist at Weill Cornell Medical College, who has
criticized vaccine trials he considered futile. "In the general HIV-
research community, I didn't know anyone who said this was going to
happen."
Both trials recruited people who were at high risk of HIV infection
through sexual activity. The STEP subjects included many male
homosexuals; the Phambili volunteers were male and female
heterosexuals. Half the people in each trial were randomly assigned to
get three shots of vaccine, and half to get three shots of a harmless
liquid containing no adenovirus or HIV proteins.
Each trial was to have 3,000 participants. STEP had finished enrolling
subjects in North and South America, the Caribbean and Australia.
Phambili (which means "moving forward" in the Xhosa language of South
Africa) had signed up 801 by the time it was shut down.
While scientists hoped the Merck vaccine might prevent some
infections, its chief purpose was to stimulate "cell-mediated"
immunity to produce a less severe illness. Specifically, the vaccine
was expected to lower the "viral load" of HIV in the bloodstream,
which in turn would both prolong survival and lessen the chance the
person would infect others.
Many experts are questioning the wisdom of that strategy, even if it
had worked perfectly. Urging millions of people to take an AIDS
vaccine that probably would not protect them from the virus, they say,
would be a hard and confusing task, even in places where the epidemic
still rages.
For the moment, that is an academic question. The vaccine failed to
achieve any of its goals.
In both studies, people who got vaccine were more likely -- not less
-- to become infected, with trends suggesting roughly a twofold risk.
In the STEP study, which has many more cases to evaluate, nearly all
that added risk was in people who had high levels of antibodies to
adenovirus type 5 before they got their first shot -- evidence they
had been previously infected with that strain. Uncircumcised men in
that group had the highest risk.
So how could this have happened?
The leading theory is that activation of the immune system, a cascade
of events that occurs naturally when a person is infected with a virus
or bacterium or gets a vaccine against one of them, in some way
increased the risk of HIV infection.
Activation causes cells called CD4 T-lymphocytes (among many other
things) to proliferate. CD4 cells are the targets of choice for HIV.
In their activated state, they are coated with molecules called CCR5
co-receptors, which HIV needs to attach itself to a cell.
The hypothesis is that people who received the vaccine had greater-
than-normal activation and consequently produced more and fatter
cellular targets for HIV. That then increased their chances of
becoming infected should they encounter the virus in unprotected
intercourse.
Two things undercut this idea.
People have been suffering immune-activating infections and getting
vaccines for years, and there has never been evidence that those
events increased a person's risk of acquiring HIV. These vaccine
trials would be odd places to first notice such a thing. Furthermore,
people in the STEP study who got the vaccine did not have more
activated CD4 cells than people who got placebo -- something that
Merck vaccine executive Mark B. Feinberg called "kind of an
interesting and unexplained observation."
"There is something very, very peculiar" going on in the vaccine
trials, said Anthony S. Fauci, head of the National Institute of
Allergy and Infectious Diseases, which sponsored them.
The multiple surprises have reminded researchers how much they still
do not know about HIV's biology. It has also focused attention on
questions they never asked.
For example, none of the monkey experiments with the Merck vaccine
subjected animals to the kind of sexual exposure that people in the
trial had -- namely, repeated encounters with low doses of HIV, with
no single exposure being especially high-risk.
Why not?
The researchers did not have any reason to believe the vaccine might
be harmful (although they acknowledged it might not be effective), and
in any case such a study would have required quite a large number of
monkeys, which are expensive to acquire and maintain for research.
Instead, researchers vaccinated a relatively small number of monkeys
with the Merck vaccine and then injected them with the monkey
equivalent of HIV in a manner that guaranteed they would become
infected. Those animals did much better over the long run than
infected but unvaccinated ones.
That was once enough to move a vaccine into human trials. But it
probably never will be again.
http://www.washingtonpost.com/wp-dyn...032003398.html
