November 8, 2009)
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Last month, news broke of
a major breakthrough in HIV research: a new vaccine that could cut the risk of
infection by a third. However, the full results of the trial have now been
published, and the news isn't as good as it first seemed.
What do we know already?
It's hardly surprising
that news of a possible vaccine was warmly welcomed. Some 33 million people
worldwide are infected with HIV, including an estimated 80,000 in the
In a press conference at
the end of September, researchers announced that a new vaccine being tested in
While the vaccine
obviously wasn't 100 percent effective, was this small difference still worth
getting excited about? The answer to this question turns on a concept called
What's a significant
Suppose your friend claims
to be able to tell the difference between Coke and Pepsi. They bet you Ł10 that
they can, and challenge you to put them to the test. You could give them samples
of both drinks, in unmarked glasses, and see if they can give you the right
answer. The problem with this test is that anyone could pass it 50 percent of
the time simply by guessing.
You could do a more
rigorous test by repeating the challenge. The chances of guessing correctly five
times in a row would by pretty slim, at around 3 percent. If your friend got it
right every time, you might decide they really could tell the difference, and
Researchers do something
similar when they analyse results from a study. They calculate the probability
that a particular result would happen by chance. Traditionally, scientists trust
a result so long as the chance of it happening by accident is less than 5
percent. If a result passes this test, it's said to be statistically
significant. This doesn't necessarily mean a big or important difference; it
just means that it's unlikely to be a fluke.
What does this mean for
the vaccine trial?
The trial results have now
been published in full, so we can see whether the small amount of protection the
vaccine seemed to offer was significant or not. The answer? No. And yes.
The researchers analysed
their results three different ways. The first included all the people who'd
taken part in the trial. Some of these people might not have had all four doses
of the vaccine, but they were treated as if they had. This is a good way of
checking how well a treatment works in the real world, where similar problems
often happen. Even in a carefully planned study like this, more than 1,000
people didn't get all four doses of the vaccine. In this analysis of the
results, the effect of the vaccine wasn't statistically significant.
Second, the researchers
looked at people who'd been given all the doses of the vaccine as planned. This
tells you how well a treatment works if given perfectly. Again, the result
The third analysis was
similar to the first, including almost everyone, but it left out seven people
who'd turned out to be HIV positive at the start of the study. Looked at this
way, the effect of the vaccine was significant.
So, did the vaccine work
It's hard to know what to
make of such borderline results. It could be that the vaccine didn't work, and
it was sheer chance that slightly fewer people got infected in the vaccine
group. Alternatively, there might be a benefit to having the vaccine, but it's
fairly small, and just on the edge of what the study was capable of detecting.
Aside from the statistics,
there are other reasons to be cautious about the vaccine. The study actually
looked at a combination of two vaccines, both of which had failed to protect
against HIV in previous studies. Researchers were hoping that they would work
better together than separately.
At best, the vaccine could
have a modest benefit. It's unlikely to play a major role in preventing the
spread of HIV. We can hope that the work done so far paves the way for a more
effective vaccine in future.
Pitisuttithum P, Nitayaphan S, et al. Vaccination with ALVAC and AIDSVAX to
prevent HIV-1 infection in Thailand.
ScienceDaily (Nov. 8,
2009) — Researchers at Yale University have developed synthetic molecules
capable of enhancing the body's immune response to HIV and HIV-infected cells,
as well as to prostate cancer cells. Their findings, published online in the
Journal of the American Chemical Society, could lead to novel therapeutic
approaches for these diseases.
The molecules -- called
"antibody-recruiting molecule targeting HIV" (ARM-H) and
"antibody-recruiting molecule targeting prostate cancer" (ARM-P) --
work by binding simultaneously to an antibody already present in the bloodstream
and to proteins on HIV, HIV-infected cells or cancer cells. By coating these
pathogens in antibodies, the molecules flag them as a threat and trigger the
body's own immune response. In the case of ARM-H, by binding to proteins on the
outside of the virus, they also prevent healthy human cells from being infected.
"Instead of trying to
kill the pathogens directly, these molecules manipulate our immune system to do
something it wouldn't ordinarily do," said David Spiegel, Ph.D., M.D.,
assistant professor of chemistry and the corresponding author of both papers.
Because both HIV and
cancer have methods for evading the body's immune system, treatments and
vaccinations for the two diseases have proven difficult. Current treatment
options for HIV and prostate cancer -- including antiviral drugs, radiation and
chemotherapy -- involve severe side effects and are often ineffective against
advanced cases. While there are some antibody drugs available, they are
difficult to produce in large quantities and are costly. They also must be
injected and are accompanied by severe side effects of their own.
By contrast, the ARM-H and
ARM-P molecules, which the team has begun testing in mice, are structurally
simple, inexpensive to produce, and could in theory be taken in pill form,
Spiegel said. And because they are unlikely to target essential biological
processes in the body, the side effects could be smaller, he noted.
"This is an entirely
new approach to treating these two diseases, which are extraordinarily important
in terms of their impact on human health," Spiegel said.
HIV is a global pandemic
that affects 33 million people worldwide, while prostate cancer is the second
leading cause of cancer-related death among American men, with one out of every
six American men expected to develop the disease.
Funding for this research
was provided by the National Institutes of Health.
By GayNZ.com Daily News
7th November 2009 - 03:54 am
wholesaler of erotica is pitted against the NZ AIDS Foundation as it encourages
retailers to stock a self-test HIV kit, the first in a projected series of home
test kits for sexually transmitted infections.
Turkana Trading says its
EZ-Trust kits, which give a result within a few minutes, will save lives by
reaching out to people who aren't testing through the usual sexual health
centres. The AIDS Foundation believes that without expert guidance and support
users of the home test kits may be headed for disaster. It yesterday called
Turkana "irresponsible and unprofessional" for distributing the
80 per cent of new, locally contracted HIV infections in
An HIV diagnosis used to be an automatic death sentence, but with advances in medications, some of which have unpleasant or even debilitating side-effects, an AIDS-related death is no longer such an inevitability. Likewise, testing for the presence of HIV, or more accurately the antibodies created by the body's struggling immune system when HIV is present, has become more straightforward. Last year the NZAF was at the forefront of NZ sexual health agencies by introducing a 'rapid test' system. A prick on the finger, a droplet of blood on a nifty little test kit and a few minutes wait can deliver an indication of the likely presence, or absence, of HIV. Sadly, it's not actually that straightforward.
LEGALITIES AND APPROVALS
Until now such kits have been exclusively used in a professional setting with pre- and post-test counseling and support instantly on tap. But they are increasingly available over the internet and, now, over the counter in
Is it legal to sell an HIV self-test kit in a non-healthcare or non-pharmacy setting? Apparently so. The NZAF advises that rapid HIV tests are considered a `medical testing device` and as such are not regulated by Med Safe, the government agency responsible for approving medications. Turkana acknowledges its Singapore-manufactured kit has not yet been assessed and approved by any
A QUALITY PRODUCT?
Turkana says their kits are of high quality and are reliable. "We have selected the best quality product from a reputable supplier," Colwill says, claiming that the results are better than 99% accurate. "This product was 400% higher in cost price than its nearest competitor," he adds.
Asked if those claims stack up, the NZAF sounds a note of caution. "The test itself is not one of which the NZAF has knowledge. It is not mentioned in any research materials that we have seen from the US Federal Drug Administration, the World Health Organisation or any other body," says Eamonn Smythe, NZAF Director Positive Health Services. "It may be a legitimate test but the distributors we have for Uni-gold and those for the Determine test, the two best testing kits in the world, only sell to health professionals, and never to end users." A promotional sheet from the manufacturer says the kit complies with the international ISO 13485 medical device standard.
DESPERATELY SEEKING ASSURANCE
Can a one-off test like EZ-Trust, which is packaged in a single test box, give any reliable assurance that a person is free of HIV infection? "No," says Smythe. "The test currently available in
That window of invisibility is an important part of the emerging controversy and worth reflecting on. A person infected with HIV may not develop antibodies for three months or so after being infected. During that time they can pass on HIV yet no currently available test will detect the virus. Only when the immune system begins to become overwhelmed by the virus and starts producing billions of HIV-specific antibodies can the tests detect those antibodies and thus indicate the presence of HIV.
All an HIV test can do is indicate whether a person contracted HIV more than three months, or so, ago. Turkana acknowledges this in a single page supplementary guide it has produced to be handed out with its pre-packaged single-test kit. After guiding purchasers to two websites, Wikipedia and the site of an organisation focused on delivery of HIV services to developing nations, for information, Turkana merely advises the user to make themselves familiar with "the HIV detection window period which can be up to three months." Further down they advise the user of their kit to seek "urgent confirmation" of a positive test by contacting a medical professional.
SUPPORT AND GUIDANCE
Lack of instant and structured support for a newly-diagnosed HIV positive person is another factor at the core of the AIDS Foundation's opposition to home testing. "The NZAF strongly supports professional HIV testing with the provision of pre- and post-testing counseling, provided by the NZAF Regional Services, your local Sexual Health Service, or GP," says Smythe. "Everyone will react in a different way to a positive diagnosis and research shows that without professional pre- and post-test counseling or psychotherapy a positive HIV test might result in depression, self harm, and [even] harm to others whom they think may have infected them."
Smythe also fears possible further transmission of HIV due to a lack of sufficient knowledge about HIV or correct use of condoms and lube, which the NZAF promotes as the only reliable way to prevent the sexual transmission of HIV between men who have anal sex with men. And he says disclosure, who and when to tell, is a significant issue requiring guidance. An ill-considered revelation of one's HIV positive status can result in "stigma and discrimination, and/or depression and isolation." Conversely, there are also issues stemming from lack of disclosure to sex partners and family as well, says Smythe.
DISCLAIMERS AND DISTANCING
A disclaimer message on the EZ-Trust kits briefly explains the three month wait needed before another rapid test is done. "If there has been a possible exposure to infected blood, and the person tests negative for HIV, the test must be repeated in 90 days." There's no mention of that other, more likely source of infection, semen. "It is imperative that a positive HIV test be followed by Elisa, a Western Blot or PCR test performed by a doctor or clinic to confirm if you are indeed HIV positive." It also acknowledges that no test or test kit is infallible.
Turkana's supplementary information sheet effectively distances the wholesaler and retailer from this whole issue. "By doing this test at home you are electing to test without associated counseling or advice," it states. "It is common practice for trained staff to advise and prepare you about the realities of a positive test result before you test. By testing yourself you are bypassing this assistance." Turkana doesn't even hint at what those realities might be, but it does list the NZAF's AIDS Hotline and the Lifeline phone counseling service as sources of information.
If still in doubt, Turkana says, the purchaser should seek medical assistance with the test, yet those same medics generally provide HIV testing for free, though GPs charge per visit and will use the Western Blot/Elisa tests which take several days to produce a result. But there may of course be a case for a person who has undertaken their first test in a supportive and informed environment to continue self-testing from time to time at home.
The final lines of Turkana's information sheet may chill the blood of those who deal with the "realities" of HIV infection: "no warranties or representations, expressed or implied, as to the accuracy" of its information sheet.
TAKING THE BROAD VIEW
Is the way this HIV home test kit, which is likely to retail for around $40 depending on individual retailer markups, is being promoted appropriate?
"Not at all," says Smythe, who views HIV testing through the NZAF's broad mandate to prevent infections and to support those already infected. "There is ample research, anecdotal evidence and the personal experience of every person living with HIV that proves that a positive test for HIV is a shocking, life-changing and often deeply traumatic experience. The NZAF is committed to providing free, professional pre- and post-test counseling and psychotherapy because effective and professional testing and services can reduce the further spread of HIV, limit the potential trauma that a positive diagnosis may cause."
Clearly on a roll Smythe rattles off more of his organisation's goals around HIV testing: to assist any person with a predictive positive result through the confirmation process; to educate anyone taking an HIV test about the relative risks of different sexual activities and safe sexual behaviour; to provide more information and education to any client with a positive result in order not only to prevent further spread, but also to facilitate the empowerment of the client. He also lists encouraging the provision of follow-up support and enable a person living with HIV to explore the options available and support them through events such as disclosing their HIV status to their partners, family, friends and employers and the referral of clients to other professional services, if needed, such as mental health and drug and alcohol services. It's a comprehensive, and wordy, set of goals, yet this is an area of work in which the NZAF is rarely if ever criticised.
With all this in mind, Smythe says, the NZAF will be contacting the Singapore-based manufacturer of the kit about "the validity of the test and their decision in choosing to sell to a non-health professional wholesaler." Although he doesn't say so GayNZ.com understands the Foundation has already voiced its concerns directly to Turkana, but any such representations haven't so far deterred the company from forging ahead to bring HIV self-testing into New Zealand homes.
Tomorrow, in part two of this feature, Turkana addresses the NZAF's concerns and explains that its objectives include enabling as many people as possible to take an HIV test in order to save lives. And we glance overseas to where several other countries are beginning to grapple with this thorny issue.
November 03, 2009: 03:37
-To tackle increasingly
diverse and complex needs of people living with HIV/ AIDS worldwide.
-Strong focus on
stimulating research and development
-ViiV Healthcare has 10
medicines currently available including therapies such as Epzicom/Kivexa (abacavir
sulfate+lamivudine) and Selzentry/Celsentri ( maraviroc).
-Revenues from these
available treatments generated sales of GBP1.6 billion in 2008.
-ViiV Healthcare has
financial stability to support sustained investment in its pipeline and
-ViiV will pursue multiple
strategies to develop this existing business and to deliver new growth
opportunities, including geographic expansion, new collaborations and business
-Also has a pipeline of
seven innovative and targeted medicines, including five compounds in phase II
Healthcare has 17 molecules in its portfolio to develop as potential new HIV
By LAURAN NEERGAARD, AP
Medical Writer Lauran Neergaard, Ap Medical Writer Thu Nov 5, 2009
The experiment marks the
first time researchers have tried that long-contemplated step in people — and
the first effective gene therapy against a severe brain disease, said lead
researcher Dr. Patrick Aubourg of the University Paris-Descartes.
Although it's a small,
first-step study, it has "exciting implications" for other blood and
immune disorders that had been feared beyond gene therapy's reach, said Dr.
Kenneth Cornetta, president of the American Society of Gene and Cell Therapy.
"This study shows the
power of combining gene therapy and cell therapy," added Cornetta, whose
own lab at
The research was published
in Friday's edition of the journal Science.
In 20 years of gene
therapy research, there have been few home runs and some headline-making
setbacks — including a risk of leukemia caused by otherwise successful gene
therapy for another rare disorder, "bubble boy disease." That's a risk
that specialists hope a lentivirus-based gene therapy will eliminate.
Best known from the movie
"Lorenzo's Oil", adrenoleukodystrophy, or ALD, is a rare genetic
disease that, in its most devastating form, destroys the coating of nerve fibers
in boys' brains. Without that coating, called myelin, the neurological system
breaks down. The disease typically strikes between the ages of four and 10,
leading to blindness, deafness, dementia and loss of muscle control, and killing
them within a few years.
Bone marrow transplants
can halt ALD by letting new myelin-forming stem cells take root. But it's
difficult to find a matching marrow donor, and the transplant itself is very
So what if stem cells from
the boys' own bone marrow could be genetically corrected, eliminating the ALD
mutation? To do that, Aubourg's team had to overcome a technical hurdle: Gene
therapy works when scientists harness deliver a healthy new gene by attaching to
a virus that can harmlessly infect cells. But none of today's so-called gene
therapy "vectors" could penetrate enough of the stem cells needed for
an ALD treatment to work.
Unlike most viruses, HIV
can penetrate stem cells, and it sticks permanently. So Aubourg's team removed
the genetic parts of HIV that make it dangerous, leaving basically a scaffolding
to carry the new therapeutic gene.
Then they culled stem
cells from two 7-year-old boys in the early stages of ALD, and mixed in the
healthy gene. The boys underwent bone marrow-destroying chemotherapy and then
had their genetically corrected stem cells reinserted.
Two years later, the boys
have shown no sign of worsening brain damage and are functioning well with 15
percent of their blood cells producing the healthy protein, said Aubourg, who
plans to test the experimental procedure in more patients. An advocacy group,
the Stop ALD Foundation, is working to raise money for a similar
06 November 2009
Researchers in the
Carboranes are polyhedral
cages composed of carbon and boron atoms. The cages can be paired through a
metal ion - in this case cobalt - to form metallacarboranes. Pavlína Rezácová,
metallaboranes are joined by a linker chain with a central quaternary
The team found that
significant inhibition of the enzyme could be achieved - with varying degrees of
potency depending on the nature of the substituent groups on the amine.
Importantly the compounds also inhibited variants of the enzyme that had
developed resistance to existing treatments.
X-ray crystallography of
the inhibitor binding to the enzyme showed that the while the molecules were
occupying the enzyme's active site, the same as existing drugs and the natural
peptide, the metallacarborane cages additionally interfered with other key parts
of the enzyme's structure.
structure of how the compounds bind to HIV protease
Based on these findings
Rezácová believes that metallacarboranes are worth pursuing as HIV protease
inhibitors. 'Their chemical and biological stability, low toxicity, and the
possibility to introduce heteroatoms into the cage or polar group modifications
to the side chains make boron clusters very attractive pharmacophores for
development of potent HIV protease inhibitors,' she says. 'In our future work we
will address the issue of optimal size and flexibility of the linker and also
focus our optimisation effort on improving physico-chemical properties of the
compounds to increase solubility and prevent aggregation.'
Celia Schiffer, a
structural biologist at the University of Massachusetts in the US with intimate
knowledge of HIV protease, says that while the metallacarboranes are weak in
comparison to the therapeutically used HIV protease inhibitors, the pattern of
their binding with highly resistant HIV protease variants 'warrants a careful
examination'. Schiffer adds, 'the way that these compounds fit in the active
site is fascinating and the work certainly points up new areas of thought.'
P. Rezácová et al., J.
Med. Chem., 2009, DOI: 10.1021/jm9011388
Friday, November 06, 2009
"AIDS drugs should be
given to all who need them to reduce new infections, the World Health
Organization said," following a three-day meeting on the topic of using
antiretroviral therapy (ART) to help prevent the spread of HIV, Bloomberg
reports. "Providing more antiretroviral drugs 'will achieve a significant
transmission benefit,' Teguest Guerma, interim director of the WHO’s AIDS
department, said … 'In the past, there has been a false dichotomy between
prevention and treatment. …'That is really what has been corrected. Prevention
and treatment are two faces of the same coin'" (Bennett, 11/5).
The meeting provided the
opportunity for health experts to "review scientific data available on the
use of ART for prevention," examine "the implications of this approach
for individuals and communities," and evaluate "human rights and
ethical and public health implications" of such an approach, according to a
UNAIDS press release. "UNAIDS strongly recommend[s] a comprehensive package
of HIV prevention approaches and advocates for an evidence informed and human
rights based approach to HIV prevention," according to the release (11/6).
The meeting came after
a Lancet study "last year suggested the spread of HIV in hard-hit
African nations could be cut by 95 percent in a decade if everyone was tested
and those found to be infected were treated immediately," Bloomberg writes.
Last week, researchers presented an article in Nature Precedings challenging
the assumptions made in the Lancet study, according to Bloomberg. "Even
under optimistic assumptions we find elimination to be unlikely," the
researchers said in their paper. "Achieving a very high treatment rate
would reduce transmission substantially, but not enough to achieve
"The so-called 'test
and treat' strategy may involve millions more people getting treatment in
nations already struggling to get drugs to those who need them," the news
service writes. "At least 5 million people with HIV in poorer nations
don’t have access to the medicines out of 9 million who need them, the WHO
said in a Sept. 30 report" (11/5).
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