Clad in a yellow
gown, blue foot covers, hair net, face mask and latex gloves, Paula Cannon
pushed open the door to the animal room. "I hate this smell," she
said, wrinkling her nose. News (Updated
August 22, 2010)
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by Savitha.C.Muppala on
August 21, 2010
A novel approach to
eliminate HIV in the host by destroying only the infected cells is an idea being
explored by scientists and if this is a success can lead to an effective
anti-HIV therapy.
Current HIV treatments do not eradicate HIV from host cells but rather inhibit
virus replication and delay the onset of AIDS.
On infection, HIV spreads through the human body after the viral DNA is
incorporated into the genome of host cells.
Highly Active Anti-Retroviral Therapy (HAART) works by blocking HIV replication
at various steps but does not eliminate the infected cells.
Professors Abraham Loyter, Assaf Friedler and their colleagues at
Loyter contends that while HIV integrates its DNA into the human genome, it only
inserts enough DNA to replicate yet avoids host genome instability leading to
programmed death of the infected cells (apoptosis).
The researchers sought to induce increased integration of HIV DNA into human
genome that could lead to apoptosis.
Toward that goal, they developed peptides (called "mix") that can
penetrate into infected cells and stimulate the activity of the viral integrase.
The stimulation of the viral integrase resulted in an increase in the number of
the viral DNA molecules integrated into the infected cells that lead the
infected cells into "panic mode", causing self-destruction.
"Whilst this research is promising, a major caveat with these studies is
that they are preliminary. So far these experiments have only been shown to
'cure' HIV from small dishes of cultured cells in the authors' laboratory, but
the findings are an exciting development in the quest to eradicate this
devastating global pandemic," said Loyter.
The study is published in BioMed Central's open access journal, AIDS Research n
Therapy.
"HIV's ability to
mutate makes it difficult to target and treat," said molecular virologist
Louis Mansky.
"We wanted to take
advantage of this behaviour by stimulating HIV's mutation rate, essentially
using the virus as a weapon against itself," Mansky added.
The two drugs, decitabine
and gemcitabine - both FDA approved and currently used in pre-cancer and cancer
therapy - were found to eliminate HIV infection in the mouse model by causing
the virus to mutate itself to death - an outcome researchers dubbed "lethal
mutagenesis."
Mansky and colleague
Christine Clouser found that the drug concentrations needed to eliminate HIV
infection cause no measurable cell toxicity and were effective against HIV
cultures at concentrations well below the current levels used for cancer
treatment.
Gemcitabine and
decitabine have been administered in pre-clinical trials with mice. Initial
findings confirm that the drugs are an effective antiviral therapy for HIV.
The researchers are now
in the process of modifying the drugs to forms that can be absorbed by the human
body when taken orally.
The findings were
recently published online in the Journal of Virology.
Published on Thu Aug 19, 2010
Health experts warned
cases of HIV/AIDS are continuing to rise, with 843 cases being treated in
The figures for the
county have risen by 35% in the past four years.
However there were fewer
new cases in 2009 than in 2008 - 106 compared to 110 - according to latest
figures from the Centre for Public Health at
In the
A total of 41% of
patients said they acquired the infections outside the
Dr Penny Cook, report
author and lead researcher, said: “The number of people in treatment for HIV
in the
“Many of the new
infections were acquired in the
“We must ensure that in
this difficult economic time resources continue to be invested in prevention,
since targeted health promotion campaigns save the NHS a substantial amount of
money in the long run by preventing new infections.”
Professor Mark A Bellis,
co-author and director of the Centre for Public Health said: “We now have a
better understanding than ever of the HIV virus and of the ways it is
transmitted between people but so far this has failed to translate into
consistent reductions in new HIV infections each year.
“As with obesity,
smoking and alcohol the challenge is now not just understanding their connection
with ill health but finding the most persuasive ways to change people’s
behaviour.”
Professor Qutub Syed,
director, HPA North West, said: “The fact that more people than ever before
are accessing care and treatment in the North West reflects the fact that modern
treatments are helping people with HIV to live normal lives for much longer than
previously.
“However, it’s
worrying that we are seeing so many new cases and that the larger proportion of
these were acquired in the
The total number of
people in treatment and care in the region has increased over five-fold since
1996. This increase is a result of a continuing high number of new infections,
881 cases in 2009, and the fact that death due to AIDS is now relatively rare.
Only 0.4% of the HIV
positive population, 24 people, died of an AIDS related condition in 2009. This
death rate is dramatically reduced from the 9% recorded back in 1996.
By Rachel Bernstein,
Story posted 2010.08.21
Clad in a yellow
gown, blue foot covers, hair net, face mask and latex gloves, Paula Cannon
pushed open the door to the animal room. "I hate this smell," she
said, wrinkling her nose.
The stink came from
scores of little white mice scurrying about in cages. Some of the cages were
marked with red biohazard signs, indicating mice that had been injected with
HIV.
Yet, in some of the
animals — ones with a small genetic change — the virus never took hold.
Like mouse, like man?
Maybe so.
In early 2007, a patient
in
It worked. Sixty-one days
after the patient's transplant, his virus levels were undetectable, and they've
stayed that way.
Since news of the man's
cure broke, HIV patients have been telephoning doctors to ask for bone marrow
transplants. But it's not that simple. The treatment is too risky and
impractical for widespread use.
"A bone marrow
transplant — it's a horrible process you would not wish on your worst enemy
unless they needed one to save their life," said Cannon, a biology
professor at USC's Keck School of Medicine. There are grueling treatments to
prepare a patient for transplant; the danger of rejecting the marrow; and the
risk of graft-versus-host disease, wherein the marrow attacks the patient.
And that's assuming the
patient can find a matching donor — a difficult proposition in itself — with
the right HIV-resistant genetic constitution, which is present in only about 1%
of the Caucasian population.
But there could be
another way.
Instead of sifting
through the sands for a rare donor and then subjecting a patient to the dangers
of a bone marrow transplant, Cannon and her colleague Philip Gregory, chief
scientific officer at the Richmond, Calif.-based biotech company Sangamo
BioSciences, began to think: They could use gene therapy instead, to tweak a
patient's own cells to resistance — and recovery.
The mouse
"cure," they say, suggests they're on the right track.
Now, with $14.5 million
from the California Institute for Regenerative Medicine, the San Francisco-based
stem cell research-funding center created by 2004's Proposition 71, Cannon,
Gregory and researchers at the City of
Cannon and other HIV
researchers insist that, despite cancers and deaths associated with past gene
therapy trials, it's the right way to target the disease. They cite recent
successes, including treatments that cured children with the "bubble
boy" syndrome and helped blind children regain their vision.
"I don't think
anyone would want to do gene therapy if there were an alternative," said
Caltech biologist David Baltimore, one of the many L.A.-based researchers
pursuing gene therapy strategies to prevent or cure HIV. "I think it's
absolutely necessary. Nothing else will work."
Since AIDS emerged in the
early 1980s, development of anti-HIV medications has turned the disease from a
virtual death sentence into a chronic, manageable condition.
But the clamor for a cure
hasn't quieted.
Vaccine trials have
failed; drug-resistant strains are on the rise; and the meds, which can have
uncomfortable side effects such as fatigue, nausea and redistribution of body
fat that creates a so-called buffalo hump, cost about $20,000 a year.
A bone marrow transplant
is about five times as expensive, but it would have to be done only once.
The question was, could
researchers create bone marrow stem cells that — just like the marrow the
In 2006, Gregory asked
Cannon if she was interested in testing whether a tool his company developed,
called a zinc finger nuclease, could do the trick.
Zinc finger nucleases are
genetic scissors, cutting DNA at a specific site — say, in the middle of the
CCR5 gene. When the cell glues the gene back together, it usually makes a
mistake, resulting in a gene that no longer works.
"It just jumped out
at me as, 'Oh my gosh, that's actually something that could work,' " Cannon
said.
The team spent about a
year optimizing the procedure for treating delicate stem cells with the CCR5
snippers.
They tested the method
using so-called humanized mice — ones engineered to have a human immune system
— because HIV doesn't infect normal mice. When stem cells were treated with
the molecular scissors before being injected into mice, the resulting immune
system lacked CCR5, exactly as the scientists had hoped.
These mice acted just
like the
Ready to make the leap
from mouse to man, Gregory found a third leg for the team: researchers at City
of
"They brought
Paula's data to us and we said, 'Wow, this looks fantastic,'" said Dr. John
Zaia, City of
Researchers there are now
working toward clinical trials, optimizing every element of the treatment for
safety, effectiveness and reproducibility.
On a wiltingly hot
afternoon in July, lab manager Lucy Brown maneuvered a computer mouse across
three screens speckled with red, yellow and green dots.
The computer was hooked
to a flow cytometer — a collection of black boxes, green wires and silver
knobs that can detect subtle differences between cells and separate them at a
rate of 50,000 per second. This is how the scientists will separate stem cells
from patients' blood once trials are underway, to be sure that the genetic fix
in the CCR5 gene was made, and kept.
Upstairs, machines with
mazes of sterile tubes and pumps stood ready to prepare cells for CCR5-snipping.
Here, the scientists will purify the bone marrow stem cells, increasing their
numbers first to 5% of total cells, up from a measly 0.1% in the starting
mixture, and then to 99%. At this point they can begin testing methods to clip
the cells' DNA.
When all is perfected,
the scientists will have a precise recipe for producing batches of engineered
stem cells, including exactly how long the cells should be treated, how much of
each chemical needs to be added, how pure the cells need to be, and thousands of
other details.
"We are literally
writing the book on how you do this," said David DiGiusto, director of City
of
To receive FDA approval
for clinical trials — a goal they hope to achieve in three to four years —
the researchers must prove that they can safely and reliably prepare the cells.
Once they get the green light, the first cases will probably be people like the
They'll modify the
patients' cells in the stringently sterile manufacturing lab that DiGiusto
designed with details such as cove molding and seamless floors so there are no
corners or cracks to collect dust. Anyone who enters must wear a full bunny
suit, much like the one Cannon wears in her mouse room, to keep from
contaminating the delicate cells.
Some have advertised the
effort as a quest for the elusive "C" word, but Cannon doesn't quite
see it that way.
"People say we're
trying to cure HIV," she said. "I think of it more as, we're just
trying to make the body live quite happily and healthily with a small amount of
virus."
rachel.bernstein@latimes.com
LOS ANGELES, Aug. 18 (Xinhua)
-- Researchers at
The researchers said they
hoped to begin human clinical trials in two to three years.
The drug, PIE12-trimer,
is ideally suited for use as a vaginal microbicide (topically applied drug) to
prevent HIV infection, the researchers said in the study appearing Wednesday in
the online issue of the Journal of Virology.
PIE12-trimer was designed
with a unique "resistance capacitor" that provides it with a strong
defense against the emergence of drug-resistant viruses.
The drug consists of
three D-peptides (PIE12) linked together that block a "pocket" on the
surface of HIV critical for HIV's gaining entry into the cell.
"Clinical trials
will determine if PIE12-trimer is as effective in humans as it is in the
lab," said Michael S. Kay, associate professor of biochemistry in the
University of Utah School of Medicine.
The study is particularly
focused on preventing the spread of HIV in
"We believe that
PIE12-trimer could provide a major new weapon in the arsenal against
HIV/AIDS," said Kay.
"Because of its
ability to block the virus from infecting new cells, PIE12-trimer has the
potential to work as a microbicide to prevent people from contracting HIV and as
a treatment for HIV infected people. HIV can develop resistance rapidly to
existing drugs, so there is a constant need to develop new drugs in hopes of
staying ahead of the virus."
Across the world, HIV
occurs in many different strains and has the ability to mutate to resist drugs
aimed at stopping it. Due to the high conservation of the pocket region across
strains, PIE12- trimer worked against all major HIV strains worldwide, from
Southeast Asia and South America to the
A collaboration of
researchers in the
The human immunodeficiency virus (HIV) is one of the deadliest pathogens on the
face of the planet, responsible for the deaths of millions of people worldwide
each year.
It is the source of AIDS
(acquired immunodeficiency syndrome), an unforgiving disease for which there is
currently no cure. For millions, contracting the disease equals a death
sentence.
This is especially true in the developing world, where limited access to drugs
and healthcare personnel, alongside other motives, prevents the general
population from getting rid of the virus and the disease.
But, even if HIV appears to destroy the human body's natural defenses,
researchers say that a immune system response of sorts exists when the pathogen
first invades.
This early innate immune response to HIV infection is the main target of the new
investigation.
Salk Institute for Biological Studies professor John Young, PhD, and
Sanford-Burnham Medical Research Institute associate professor Sumit Chanda, PhD
are the leaders of the multi-institutional team in charge of carrying out the
research.
Their work is sponsored with a $21 million Program Project Grant.
“More traditional approaches have relied upon investigating the roles played
by single genes or individual cellular pathways. While these studies have borne
some fruit, they only uncover small pieces of a highly interconnected
network,” Young explains.
He is the director of the Nomis Foundation Laboratories for Immunobiology and
Microbial Pathogenesis at the Salk Institute.
“The team working on this grant wants to understand how the innate immune
system functions as a whole, with the goal of building accurate mathematical and
experimental models that can ultimately be used to inform vaccine design and
used to predict which cellular factors represent new targets for antiviral
therapies,” he adds.
“The project may also reveal why some individuals differ in their
susceptibility to HIV infection,” Young believes.
“The events that occur immediately after exposure to HIV, which determines the
ability of the virus to establish infection and ultimately shape the course of
the disease, are very poorly understood,” Sumit Chanda concludes.
Deaths rise and studies
suggest one in six people are unknowingly carrying hepatitis B or C
Sarah Boseley
The Guardian, Wednesday
18 August 2010
The NHS is being urged to
offer free high-street pharmacy tests for hepatitis B and C, which cause liver
diseases including cancer, following studies showing that one in six people are
unknowingly carrying one of the viruses.
Pilot studies last year
in 19 pharmacies in five areas in the
The pharmacies ran 236
tests, and found 35 people with hepatitis C (15%) and four with hepatitis B
(2%). The GP diagnosis rate was 4% and 2% respectively.
Death rates from
hepatitis are rising, said Charles Gore, chief executive of the Hepatitis C
Trust. "It is a tragedy that increasing numbers of people with hepatitis B
and C are dying, often from particularly unpleasant liver cancer which these
viruses can cause. It is a tragedy because they have generally been living with
the virus for years and could have been given treatment at any point, if only
diagnosed. So we desperately need new approaches to testing that will find the
undiagnosed patients. This pilot study shows pharmacy testing could be just what
is needed."
The trust, with the Royal
Pharmaceutical Society, is calling for primary care trusts to find the necessary
funds to pay pharmacies to offer the tests to customers.
Hepatitis infection is
symptomless in its early stages. The viruses are transmitted primarily through
blood. Intravenous drug users are at high risk if they share needles. Some
people were infected after receiving contaminated blood transfusions prior to
1991, when all blood products began to be screened.
Those who have surgery,
medical or dental treatment, including injections, in parts of the world where
sterilisation procedures are not efficient, are also at risk. Hepatitis C can
also linger in dried blood on clippers, scissors and razors in barber shops and
hairdressers, and can be transmitted between people who regularly share razors.
Even sharing toothbrushes can be a danger if the gums bleed.
Some of the pilot testing
took place on the
"The results speak
for themselves, pharmacies see a different cohort of people to [those who visit
GPs] and therefore we can access and diagnose people who otherwise would not
have been tested," said Gary Warner, from Regent Pharmacy, on the island.
"This scheme has woken a lot of people up to the problem of viral hepatitis
and we are now working with local drug and addiction services in a more
integrated way than before."
Early treatment can clear
the hepatitis C virus from about half of all patients, and the ongoing infection
in the rest can be managed. Without detection and treatment hepatitis C can
cause cirrhosis, liver damage and death. Hepatitis B can also be sexually
transmitted. Treatment can manage the condition but not clear the virus.
Biotech drug maker Gilead
Sciences Inc. spent $350,000 lobbying the federal government in the second
quarter, according to a disclosure form.
The spending marks a 21
percent boost from $290,000
The company, based in
Besides Congress, the
company lobbied the departments of Commerce, Health and Human Services, and the
Department of Veterans Affairs in the April-to-June period.
Michael Carter
Published: 19 August 2010
There is no evidence that
starting antiretroviral therapy leads HIV-positive injecting drug users to have
more risky sex, Canadian researchers report in the online edition of AIDS. There
was no increase in reported sexual activity, unprotected sex, or number of
partners.
“Concerns regarding the
expansion of access to ART [antiretroviral therapy] for IDU [injecting drug
user] populations due to fears of increased HIV risk behaviour in the period
following ART initiation are unsupported,” comment the investigators.
Treatment with
combination antiretroviral therapy can significantly increase the prognosis of
HIV-positive individuals. Such treatment can also dramatically reduce the risk
of transmission of the virus to HIV-negative individuals.
HIV treatment can work
well in injecting drug users. However, some doctors are reluctant to initiate
treatment in drug users. This is because of a fear that this group of patients
may not adhere to their treatment.
Moreover, some research
has pointed to increased levels of sexual risk taking amongst individuals after
they start HIV treatment.
Therefore investigators
from AIDS Care Cohort to Evaluate Exposure to Survival Services (ACCESS) in
At baseline, 72% of
patients reported that they had had sexual intercourse in the preceding six
months. Recent unprotected anal or vaginal intercourse was reported by 35% of
individuals, and the median number of reported sex partners was one.
There was no evidence
that starting HIV treatment increased sexual activity. Just over a quarter (51)
of the patients who had initiated antiretroviral therapy reported any sexual
behaviour in the preceding six months.
Moreover, starting
treatment with anti-HIV drugs did not increase the risk of engaging in
unprotected sex. Anal or vaginal sex without a condom was reported by 17% of
patients in the six to twelve months after the initiation of antiretroviral
therapy.
Nor did the initiation of
HIV treatment increase the risk of having multiple sex partners. Just over a
quarter of individuals taking antiretroviral therapy reported having two or more
sex partners in the six to twelve month period after they started this
treatment.
The investigators then
performed a series of sensitivity analyses. They found no evidence that a higher
CD4 cell count after starting treatment was associated with either unprotected
sex or a greater number of sex partners.
Nor did sexual risk
behaviour increase in the longer term. There was no increase in overall sexual
activity in the two years after HIV treatment was started, and the proportion of
patients reporting unprotected sex or multiple partners remained stable.
“ART initiation was not
associated with increases in sexual activity or risk behaviour. Given these
findings, concerns regarding potential increases in or resumption of sexual risk
behaviour among IDUs following the initiation of HIV therapy appear to be
unfounded,” comment the investigators.
However, the
investigators did find other factors were associated with sexual risk taking in
the period after HIV treatment was started. Unprotected sex was associated with
having a partner (p < 0.001), sex work (p < 0.001), and syringe
sharing (p < 0.001). Having multiple partners was associated with older age
(p < 0.001), female sex (p < 0.001), crack or heroin use (both p <
0.001), and syringe sharing (p < 0.001).
The investigators
“recommend the immediate implementation and evaluation of novel programmes to
reduce barriers to HIV care and increase uptake of ART among IDUs”.
Reference
Marshall BDL et al. No
evidence of increased sexual risk behaviour after initiating antiretroviral
therapy among people who inject drugs. AIDS 24: online edition, DOI: 10.
1097/QAD.0b013e32833dd101, 2010.