News (Updated June 15,
2003)
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Thu Jun 12, 3:26 PM ET
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By PAUL RECER, AP Science Writer
WASHINGTON - The ancestry of the virus that
caused the AIDS epidemic has been traced to two strains of virus found in
monkeys in Africa.
The viruses probably passed into chimpanzees when the apes ate infected
monkey meat, researchers say.
Earlier studies have shown that HIV1, the virus that causes the most common
form of human AIDS, originated from a simian immunodeficiency virus, or SIV,
that is found in chimpanzees. But how chimps came to have SIV has been a
mystery.
American and English researchers analyzed the genetic pattern of a number of
SIV strains in African monkeys and concluded that at least two strains found in
the red-capped mangabeys and in the greater spot-nosed monkeys in south-central
Africa combined to form the type of SIV now found in African chimps.
It was this form of SIV that spread into the human population to start the
HIV1 epidemic that has killed millions of people, researchers report Friday in
the journal Science.
"The recombination of these monkey viruses happened in chimpanzees and
the chimp transmitted it to humans on at least three occasions," said
Frederic Bibollet-Ruche, a virologist at the University of Alabama, Birmingham,
and a co-author of the study. "The transfer between chimps and humans
probably happened before 1930."
Bibollet-Ruche said that three types of HIV1, called M, N and O, probably
were transmitted from chimps to humans decades ago. A second type of AIDs,
called HIV2, is known to have been transmitted from the sooty mangabey in West
Africa to humans directly, without going through the chimp.
Monkeys and chimps both represent a reservoir of SIV viruses that could, in
theory, be spread to humans, forming a new type of immunodeficiency disease, he
said.
The viruses were most likely spread from species to species when chimps eat
monkey meat and hunters in Africa eat chimp meat, Bibollet-Ruche said.
"Chimps are known to hunt and eat whatever monkey species they can
catch," he said.
As for humans, Bibollet-Ruche said "it is not such a good idea to hunt
and eat monkeys. There is a risk for humans to come into contact" with a
new form of HIV.
Bibollet-Ruche said the genetic studies suggest that lower monkeys first
became infected with SIV 100,000 years ago or even earlier.
SIV was passed to chimps after the animals split up into different subspecies
living as separate bands in West Africa and in southern and central Africa. He
said the easternmost subspecies of chimps is infected with SIV, but the virus
has not been found in chimp tribes in West Africa.
Although SIV can infect chimps and the lower monkeys, the virus does not
cause disease in those animals. Bibollet-Ruche said that the virus attacks the
white blood cells, called CD4 cells, but it does not make the animals sick or
cause a decline in their white blood cells.
In humans, HIV attacks and kills white blood cells and eventually overwhelms
the body's ability to replace them. Without these disease-fighting white blood
cells, the body becomes defenseless against infections that are easily
controlled by the by the immune system in healthy people.
Elizabeth Bailes of the University of the University of Nottingham in the
United Kingdom is the first author of the study. The other co-authors are from
Duke University, the University of Montpellier in France and the Tulane National
Primate Research Center in Covington, La.
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Thu Jun 12, 5:25 PM ET
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By Keith Mulvihill
NEW YORK (Reuters Health) - Scientists announced
Thursday that their research into the a particular type of gene therapy raises
important questions about the safety of using retroviruses to carry genes into
people.
In gene therapy, a vector -- usually but not always a virus -- is used to
carry a healthy gene into the cells of patients. If it works correctly, the
virus inserts its DNA and the new gene into cells and corrects the genetic
defect.
Earlier this year the Food and Drug Administration halted certain gene
therapy trials after two boys in France developed leukemia while they were
taking part in a gene therapy trial that aimed to bolster bone marrow with
genetically engineered immune cells. The treatment appeared to be working
remarkably well in 10 of the group of 11 boys who had a hereditary disease that
left them without an immune system.
The leukemia cases prompted researchers to speculate that the retroviral
vector used in the trial may have been integrated near a known cancer-promoting
gene.
In the current study, lead investigator Dr. Shawn M. Burgess and colleagues
analyzed where in the human genome ( two types of retroviruses are likely to
permanently integrate.
The researchers looked at one of the most commonly used retroviruses in gene
therapy -- murine leukemia virus (MLV), a mouse virus that can infect human
cells. And they also looked at another retrovirus -- HIV.
"MLV was used in the French study where two children, of 11, developed
leukemia," said Burgess.
Burgess's team looked at 903 MLV and 379 HIV-1 integrations and found two
different results for the two viruses. "This was unexpected," he said.
"HIV-1 likes to integrate anywhere in genes, and MLV likes to integrate
around the beginning of genes where the important regulatory sequences
are," he explained.
The main finding, according to Burgess, is that viruses integrate into
sequences non-randomly and it appears that every virus will do this differently.
"Thus, nothing about the safety of a particular retroviral treatment can
be assumed," he said.
In the past the assumption was that the integrations were random and that the
risk was low that the virus would integrate somewhere risky in the DNA code,
noted Burgess, who is with the National Human Genome Research Institute in
Bethesda, Maryland.
"This is apparently not true," he said.
What's more, the findings seem to jibe with what happened in the two children
who developed leukemia.
"The integrations that are believed to cause the problems both fit the
favorite-site profile we determined for MLV," Burgess said.
"Thus, the risks must be higher than we originally thought," he
added.
Burgess noted that the findings, which are published in the journal Science,
are the first-ever documentation of a large number of integration sites for two
viruses showing they behave very differently and there are inherent risks in
using them for gene therapy.
As such, he recommends that "any new vector should be profiled to
determine the integration biases of the vector to be used to help evaluate
relative risk."
The new discovery may very well be a set-back for gene therapy, as there are
few alternatives to using retroviruses as vectors, according to Burgess.
"None of (the other types) are as far along as the retroviral
vectors," he said. "They all have their own problems that are even
larger than the viruses."
"At the moment, (retroviral vectors) still seem the most promising, even
with the associated risk," he added.
SOURCE: Science 2003;300:1749-1751.
| Science - Reuters |
LONDON (Reuters) - Britain is in the grip of a sexual health crisis with cases of diseases like syphilis and gonorrhea soaring, a parliamentary committee said on Wednesday. There are now more HIV patients in Britain than ever before, the Health Select Committee said in a report but it is much "older" sexually transmitted diseases that have exploded in recent years. "I do not use the word lightly but during the course of this inquiry it has become plain that with sexual health we are looking at a public health crisis," said David Hinchliffe, chairman of the committee and a member of Prime Minister Tony Blair's ruling Labour Party. The legislators said 10 percent of sexually active women are infected with chlamydia, syphilis rates have leapt by 500 percent in the last six years and incidences of gonorrhea have doubled over the same period. Rates of teenage pregnancy were the highest in Europe. The committee said there were a number of underlying problems -- a failure of the state health service to recognize sexually transmitted diseases, other than HIV/AIDS, as a serious problem, a lack of political leadership over many years and a consequent lack of resources and strategy. The report called for sex and relationship education to become part of the national curriculum in schools, and for the introduction of a set of health service guidelines in sexual health care. The Health Protection Agency confirmed that trends in sexual health care were continuing to decline. New diagnosis of chlamydia had increased 10 percent from 64,800 in 2000 to 71,125 in 2001, and in the same time period gonorrhea increased by 7 percent from 21,131 to 22,697 and syphilis by 119 percent from 327 to 715. Dr Kevin Fenton, head of the agency's HIV and sexually transmitted infections (STI) division, added in a statement: "The rise in HIV infections has also continued with 5,300 new HIV diagnoses reported so far for 2002. When all reports are received, this figure is expected to reach 6,600, which is a 26 percent increase on 2001. "These rises have led to an increase in workload for genito-urinary medicine clinics up by 17 percent from 1996 to 2001. Delays in treatment can result in a risk of infection spreading to a wider group of sexual partners and exacerbating the problem." The Royal College of Physicians said services were collapsing under the weight of demand. Clinics were having to close their doors half-an-hour after opening due to the large amount of people waiting to be seen. Many patients were waiting 3-4 hours, causing so much frustration fights sometimes broke out.
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| Press Release | Source: Vertex Pharmaceuticals Incorporated |
Wednesday June 11, 4:00 pm ET
908 is an investigational HIV protease inhibitor being evaluated for dosing once or twice daily without food or water restrictions. The 908 compound was co-discovered by GSK and Vertex Pharmaceuticals.
To understand the potential cross-resistance of 908 to other PIs, clinical isolates containing mutations selected in patients experiencing virologic rebound on unboosted 908 in the NEAT study (V32I+I47V, I54L/M or I50V) were chosen from a database of patient samples, and susceptibility to all marketed PIs was assessed.
Approximately 16,000 HIV clinical samples from the ViroLogic database, with matching genotypes and phenotypes, were examined to identify samples with primary mutational pathways (noted above). Samples with mixtures at specific amino acids were excluded, as were samples that also contained certain primary protease mutations that would indicate prior exposure to PIs.
The selection of certain mutational pathways (V32I + I47V, I54L/M or I50V) decreased susceptibility to amprenavir, ritonavir, and nelfinavir, but maintained susceptibility to lopinavir, saquinavir, and boosted indinavir. For the viruses identified, those with V32I+I47V, I54L/M and I50V had median fold-changes to 908 of 3.4-fold, 3.6-fold and 20-fold, respectively. For these same mutations, the median fold-change for saquinavir (0.5, 1.0 and 1.2 respectively) and indinavir (2.5, 1.3 and 1.0 respectively) were below the biological cut-off. The median fold-changes were also below the clinical cut- off for lopinavir (2.9, 1.5 and 8.2, respectively). The median fold-changes for nelfinavir were 3.0, 3.6 and 2.2. Low-level cross-resistance was seen for ritonavir, with fold-changes of 3.4, 2.9 and 6.8. In this database analysis, HIV clinical isolates with mutational patterns associated with those selected by 908 retained sensitivity to lopinavir, saquinavir, and boosted indinavir; however, the clinical significance of these resistance data are currently under evaluation.
"We are in an era in HIV therapy where understanding resistance and managing the sequence of treatment is critical," said Doug Manion, Vice President of GlaxoSmithKline HIV Clinical Development.
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Mon Jun 9, 2:37 AM ET
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By JEFFREY McMURRAY, Associated Press Writer
WASHINGTON - The World Health Organization 's
long-held position that dirty needles cause 2.5 percent of African HIV exposures
is too conservative, says a leading researcher at the U.N. agency, prompting
questions about a congressional bill focused mainly on unsafe sex.
Health and Human Services Secretary Tommy Thompson has launched a review of
all research linking AIDS and medical injections, possibly laying the groundwork
for changes in how the legislation's $15 billion in funding is distributed. Sen. Jeff Sessions, R-Ala., a member of the Senate's health panel, requested
the review after he turned up a WHO report listing four separate studies that
find dirty needles responsible for 8, 15, 41 and 45 percent of exposures in
sub-Saharan Africa.
The report, dated Dec. 19, 2002, concludes that "the lowest attributable
fraction calculated on the basis of the data provided by the authors (8 percent)
exceeds our 2.5 percent modeled attributable fraction, suggesting that our
estimate is conservative."
Yvan Hutin, a WHO researcher who wrote the report, acknowledged the 2.5
percent number was probably low, although just how low remains a point of
debate. Regardless, he said, it would be wise to consider an education campaign
on unsafe needles, perceived by many as an easier and cheaper problem to correct
than unsafe sex.
"It remains a very good investment to do injection safety," said
Hutin, reached at WHO headquarters in Geneva. "It doesn't matter whether
it's 2.5 percent or more or less."
Sessions, however, contends it would have mattered while Congress was
balancing the spending priorities in the AIDS bill, which President Bush signed
last month. If the widely recognized figure was even a little higher, he said,
Congress would have poured far more money into needle education — and possibly
even a clean-needle exchange program.
But some at WHO say cost isn't the only issue. Because it is widely believed
that sex is more responsible for AIDS than needles, they contend the message
would be diluted if needle and sex education were given equal weight.
"We'd all like to see there be no unsafe injections," said George
Schmid of WHO's Department of HIV/AIDS. "But to begin to place a large
emphasis on the unsafe injections, which likely would be at the expense of
resources devoted to unsafe sex, would be an unwise decision. We need to keep
the resources where the problem is."
That position outrages Sessions, who suspects it's the reason WHO continues
to tout an estimate its researchers acknowledge is low.
"This is hogwash," he said. "It's about numbers. It's about
infections. You can certainly carry two messages. This is a life-and-death
issue. Whatever bureaucratic objections are occurring here have got to be
overcome because people are dying every day."
A major part of the AIDS bill could be rerouted if new research about
injections surfaces, Sessions said. But HHS officials aren't saying how likely
that is, or even when the study is expected to be finished.
"Like Sen. Sessions, we too are interested and concerned with how AIDS
is actually transmitted," said HHS spokesman Bill Pierce.
Sessions' interest in the connection between AIDS and injections was
heightened in March after he invited Dr. David Gisselquist to testify to the
Senate. After reviewing some 19 years of research, Gisselquist concluded that at
least one-third of AIDS exposures in sub-Saharan Africa are due to contaminated
needles in medical treatment.
Gisselquist contends that because WHO's focus has been on unsafe sex for so
long, it's deliberately overlooking good research like his. But although Hutin
now doubts the 2.5 percent number, he says Gisselquist's estimate is inflated.
"If WHO says we should put more emphasis on health care risks, people
will say, 'Why didn't you do it the last 15 years?'" Gisselquist said.
Similar concerns are raised by Gary Cohen, president of BD Medical Systems, a
New Jersey-based company that makes disposable syringes that permanently lock
after they're used once. The syringes cost about 6 cents each, he said.
For $75 million to $100 million a year, Cohen said, all of Africa could be
supplied with the safe syringes. He contends that a needle distribution program
is the most effective way to combat the problem because many people in Africa
don't have the option to demand clean needles.
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Thu Jun 12, 4:57 PM ET
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By Paul Simao
ATLANTA (Reuters) - More than two decades after
HIV first surfaced in the United States, slightly less than half of American
adults between the ages of 18 and 64 say they have been tested at least once for
the virus that causes AIDS.
The finding, based on data collected in 2001 by the U.S. Centers for Disease
Control and Prevention, indicates that AIDS tests have become a more routine
medical procedure even among those at low risk for the deadly disease.
Only 38 percent of Americans in 1994 reported ever having been screened for
the infection.
"When you look at the prevalence of testing in the general population it
has slowly increased over time, and that is good news," said Amy Lansky, an
epidemiologist in the CDC's division of reproductive health.
Although the AIDS testing rate was largely unchanged from 2000, Lansky said
it could be expected to rise in the next few years as screening was expanded in
doctors' offices and primary care facilities.
The CDC recently recommended AIDS tests become a standard part of health care
for pregnant women, intravenous drug users, anyone who engaged in unsafe sex and
infants born to mothers who had not been tested for the disease.
Such screening had previously only been advised for those visiting acute care
hospitals with a high incidence of HIV cases and for patients in clinics that
specialized in treating sexually transmitted diseases.
Making AIDS tests more common is at the heart of the CDC's strategy to
increase the proportion of HIV-infected persons who are aware that they carry
the virus from 70 percent to 95 percent by 2005.
As many as 30 percent of the estimated 850,000 to 950,000 people living with
the virus in the United States do not know that they are infected. About 16,000
Americans die each year from AIDS and another 40,000 become infected with HIV.
The Atlanta-based CDC does not have a target for AIDS testing for the general
public. "We need to focus prevention efforts on those at highest risk, so
you wouldn't necessarily expect that everyone should be tested," Lansky
said.
The District of Columbia led the nation in testing with a rate of 65.3
percent of adults between 18 and 64 reporting at least one screening for AIDS.
South Dakota had the lowest rate at 31.5 percent.
Wednesday June 11, 6:00 am ET
This multi-center, open-label clinical trial is expected to enroll up to 18
patients with HIV who have an extensive treatment history but whose virus is
no longer suppressed by highly active antiretroviral therapy (HAART). Patients
are expected to receive two monthly doses of the MDX-010 antibody in this
dose-escalation study. The trial is designed to establish safety and
tolerability of MDX-010 in patients infected with HIV, and to preliminarily
evaluate clinical efficacy. The trial will include assessments of viral load
and CD4 counts in patients, as well as immune responses to HIV and other
antigens. "We believe that MDX-010 is showing promise in cancer treatment, and
that it may also have the potential to enhance the immune systems of AIDS
patients," said Donald L. Drakeman, President and CEO of Medarex.
"The ability to boost the potency of the cellular immune response
against HIV could be crucial in allowing patients to control the virus with
their own immune systems," said Israel Lowy, M.D. Ph.D., Director of
Infectious Diseases at Medarex. "If MDX-010 can boost anti-HIV immunity,
this may allow patients to require less medication, or perhaps be weaned from
the necessity of lifelong HAART, with its attendant challenges of treatment
toxicities and requirements for strict adherence."
About MDX-010 and HIV
CTLA-4 is believed to be an important molecule in regulating an immune
response. Expressed on CD4 and CD8 T cells, CTLA-4 is believed to be
responsible for suppressing the defensive activities of these T cells against
disease or infectious agents. In HIV-infected patients, where T cell response
is poor in controlling the virus, excess amounts of CTLA-4 have been found on
the T cells; this overexpression of CTLA-4 may facilitate susceptibility to
the HIV virus and contribute to the immune suppression found in AIDS patients.
Pre-clinical studies have shown that blocking CTLA-4 with an antibody can lead
to potent immune responses to various types of viruses, bacteria and cancer.
MDX-010 is a fully human anti-CTLA-4 antibody. By blocking the suppressive
activity of CTLA-4 in HIV-infected patients, MDX-010 may enhance an anti-HIV
immune response and the ability to control HIV.
According to the Centers for Disease Control, at the end of 2001 there were
160,000 people in the U.S. living with HIV infection and 342,000 living with
AIDS.
About MDX-010 and Cancer
The use of MDX-010 to block CTLA-4 also has the potential to enable the
immune systems of cancer patients to more effectively fight tumors. MDX-010 is
currently in multiple Phase II clinical trials to test the product for use in
patients with melanoma and prostate cancer. A webcast presentation discussing
the potential use of MDX-010 to treat cancer can be found at www.medarex.com/Investor/Webcasts.htm.
Press Release
Source: Medarex, Inc.
Medarex
Initiates Phase I Clinical Trial of MDX-010 in HIV