AIDS vaccine trials - Test subjects may have been put at extra risk of contracting HIV

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more on the story reported on in the last few months...............

" 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. "

" 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. "

I suggest there are a lots of questions they never asked.

" 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. "

Now why would a vaccine be harmful? (facetious)

Well, shows you how little they know and HIV has

never been proven to cause AIDS anyway

http://www.wellwithin1.com/AIDS.htm

Sheri

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Setback in AIDS fight

Test subjects may have been put at extra risk of contracting HIV

By Brown

The Washington Post

updated 2:05 a.m. ET, Fri., March. 21, 2008

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.

'Catastrophe'

" This is on the same level of catastrophe as the

Challenger disaster " that destroyed a

<http://www.washingtonpost.com/ac2/related/topic/NASA?tid=informline>NASA

space shuttle, said Gallo, co-discoverer

of the human immunodeficiency virus (HIV), which

causes AIDS, and head of the Institute for Human

Virology in

<http://www.washingtonpost.com/ac2/related/topic/Baltimore?tid=informline>Baltim\

ore.

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

<http://www.washingtonpost.com/ac2/related/topic/South+Africa?tid=informline>Sou\

th

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

<http://www.washingtonpost.com/ac2/related/topic/National+Institutes+of+Health?t\

id=informline>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, " C. Desrosiers, a molecular

geneticist at

<http://www.washingtonpost.com/ac2/related/topic/Harvard+University?tid=informli\

ne>Harvard

University, declared last month at an AIDS

conference in

<http://www.washingtonpost.com/ac2/related/topic/Boston?tid=informline>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.

'Stop and reassess'

" 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

<http://www.washingtonpost.com/ac2/related/topic/+P.+?tid=informline>Jo\

hn

P. , 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

<http://www.washingtonpost.com/ac2/related/topic/South+America?tid=informline>So\

uth

America, the

<http://www.washingtonpost.com/ac2/related/topic/Caribbean?tid=informline>Caribb\

ean

and

<http://www.washingtonpost.com/ac2/related/topic/Australia?tid=informline>Austra\

lia.

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.

How did it happen?

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. "

'Something very, very peculiar'

" There is something very, very peculiar " going on

in the vaccine trials, said 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.

© 2008 The Washington Post Company

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Sheri Nakken, former R.N., MA, Hahnemannian Homeopath

Vaccination Information & Choice Network, Nevada City CA & Wales UK

Vaccines -

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