News (Updated May 2,
2005)
[Home]
[Previous
news]
Sun Apr 24, 5:08 PM ET
Sometimes the shortest route to a goal is not a straight line, as two intriguingly-curved paths in AIDS research show.
The classic drug strategy for combatting the human immunodeficiency virus (HIV) is head-on: hunt for a molecule that locks on to proteins on the viral surface and stops it infiltrating or replicating in immune cells.
The problem, though, is that HIV has a very short life-cycle. As it replicates, it often mutates, and thanks to Darwinian pressures, the surface proteins that emerge can be a different shape, sidestepping the designed drug.
This weasel-like ability is called drug resistance, and is one of the biggest problems facing the 40 million HIV-infected people in the world today.
Only a tiny number of very cheap drugs is available in the rollout of antiretroviral treatments in poor countries. So a resistant virus means that patients are forced to use more expensive options to treat it -- or go without.
Frustrated by the direct approach, scientists are more and more taking a sideways look at how HIV can be attacked.
One of these focuses is not on HIV itself but its target -- the CD4 T cell, which the virus hijacks in order to replicate itself and which it wrecks in the process, eventually exposing the body to opportunistic disease.
One promising discovery has been made by a US-based team led by Warner Greene at the Gladstone Institute of Virology and Immunology, part of the University of California at San Francisco.
They noted that "resting" CD4 cells -- cells that drift around the bloodstream, waiting to be called to action against a microbial intruder -- are strangely impervious to HIV infection, whereas activated cells are vulnerable.
The answer, Greene's team found, lay in a protective enzyme called A3G.
While resting, the dormant cells are shielded by a shortened form of A3G.
After activation, A3G changes form. It becomes longer, loses its protective role and the cell thus becomes vulnerable to the AIDS virus.
"Until now, the prevailing belief has been that HIV failed to infect resting T-cells due to a simple lack of some essential factor or nutrient," says Greene.
"This study now shifts the paradigm... in resting CD4 T cells, the small enzymatically active form of A3G stops the virus in its tracks."
Two potential therapy avenues open up from this discovery. One is to look for molecules that break down the large A3G complex so that the shield remains intact after cell activation; the other is to stop the A3G changing form when the cell is awoken from its "resting" state.
A different tack is being taken by British scientists, who are looking at ways of making an HIV-infected cell self-destruct.
Their target is a cell protein called ATM, which plays a vital role in cell repair.
HIV hijacks the cell's machinery by breaking open the cells' DNA and inserting itself in it.
Aware of the break-in but unaware of the violator, ATM orders repair molecules to fix the cut, thus enabling HIV to settle into the host's genome.
By scanning a library of compounds, the scientists found a compound to inhibit ATM. The genome break thus goes unrepaired, and this triggers a well-known process whereby the cell destroys itself rather than replicate with a flawed genetic code.
The team, led by Mark O'Conor, of KuDOS Pharmaceuticals in Cambridge, England, have successfully tested the KU-55933 ATM-inhibitor on cells in a lab dish.
HIV-infected cells were blocked from replicating. Two standard anti-retroviral drugs encountered resistance problems in the same tests as the virus replicated, but the inhibitor did not -- it performed with the same efficacy against all strains of the virus.
In both areas of research, big caveats are needed. The successes so far have been conducted only on cells in a lab dish, not on animals, let alone humans.
There are many safety considerations to overcome, not least the worry that inhibitors might cause chromosomal damage in CD4 cells, possibly leading to cancer.
Even so, the oblique strategy is starting to bear fruit. Even though the war on AIDS is nearly 24 years old, new fronts can be opened up against an old, crafty foe.
Thu Apr 28, 2005 04:33 PM ET
NEW YORK (Reuters Health) - Delayed diagnosis of HIV infection continues to be a
problem among gay men in England and Wales, investigators with the Health
Protection Agency's Center for Infections in London warn.
"Early HIV diagnosis is critical in getting HAART started, which is vital for survival and is likely to limit the spread of infection," Dr. Timothy R. Chadborn told Reuters Health. "However, we estimated that almost one third of newly diagnosed homosexual men were diagnosed late with HIV between 1993 and 2002."
The findings are based on over 14,000 case reports of men who have had sex with men.
Overall, homosexual men diagnosed late were about 10 times more likely to die within 1 year of their HIV diagnosis, according to a report in the March 25th issue of AIDS.
In 2001, one in four HIV-infected homosexual men in England and Wales were diagnosed late and 10 percent died within 1 year compared with less than 1 percent of those not diagnosed late.
In 2001, early diagnosis of HIV infection among homosexual men could have reduced the number of infected men who died within 1 year of diagnosis by 84 percent, and could have reduced all deaths related to HIV within 1 year by 22 percent.
"These results support recommendations for increased HIV testing for all men, alongside targeted, awareness-raising promotions," Chadborn said.
SOURCE: AIDS March 25, 2005.
Tue Apr 26, 2005 03:01 PM ET
By Amy Norton
NEW YORK (Reuters Health) - Many young gay and bisexual men who are HIV-positive may not know they have the virus, according to U.S. health officials.
Their study of more than 5,600 men between the ages of 15 and 29 found that more than three-quarters of those who tested positive for HIV were unaware they were infected. Moreover, before being tested, a majority of these men thought themselves at low risk of having the AIDS virus, and half had had unprotected sex with another man during the previous 6 months.
The findings suggest that the HIV epidemic among young gay and bisexual men "continues unabated," in part because many are unaware of their infection, according to the study authors, led by Duncan A. MacKellar of the Centers for Disease Control and Prevention (CDC) in Atlanta.
He and his colleagues report the findings in the Journal of Acquired Immune Deficiency Syndromes.
The high rate of unrecognized HIV infection seems to stem in part from a low rate of regular testing for the virus, MacKellar told Reuters Health.
Though many men in the study had undergone HIV testing in the past, few got themselves tested regularly. And only a minority of those who were unaware they were HIV-positive had been tested in the past year. It's recommended that people at high risk of HIV be tested for the virus and other sexually transmitted diseases at least once a year.
The reason for the lack of regular testing is unclear, but the fact that many men in the study believed they were at low risk for HIV may be one factor, according to MacKellar. However, he added, the findings also suggest that limited access to healthcare and fear of testing positive may be important reasons as well.
The study included gay and bisexual men who were recruited from various venues, including bars, parks, cafes and stores, in 6 U.S. cities. The men were surveyed about their sexual behavior, their perceptions of their own HIV risk and how many times they had been tested for the virus. They also gave blood samples for testing.
Overall, 10 percent were found to be HIV-positive, 77 percent of whom had been unaware they were infected.
Because of the study's recruiting method, the numbers are probably not reflective of gay and bisexual men across the U.S., according to the researchers. Previous household-based studies have, in fact, found lower rates of unrecognized HIV infection.
Still, MacKellar said the fact that so many men in this study were unaware of their infection "underscores the urgency" of increasing HIV testing among young men who have sex with men.
Expanding HIV testing at venues such as clubs and bars may help reach more men with unrecognized infection, the researchers suggest. Health departments and community groups are working to expand such outreach programs and trying to ensure that people actually get their test results by using newer, rapid HIV tests that provide results in 20 minutes.
It is also important for individual doctors to routinely recommend HIV testing to patients who might be at increased risk, according to MacKellar. "CDC is working with providers to make HIV testing a more routine part of healthcare," he said.
SOURCE: Journal of Acquired Immune Deficiency Syndromes, April 15, 2005.
Wed Apr 20, 2005 11:25 AM ET
WASHINGTON (Reuters) - The virus that causes cervical cancer can be reactivated
after lying quiet in the body for years, which can help explain why HIV-infected
women are vulnerable to the cancer, U.S. researchers reported on Wednesday.
Their study of 2,500 women who were examined every six months for an average of seven years showed those infected with the AIDS virus were much more likely to also be infected with the human papilloma virus, or HPV, which is the main cause of cervical cancer.
Most of the women became infected with HPV at some point, but it became undetectable later, apparently because the immune system can control it. There is no cure for infection with HPV, which is usually transmitted sexually.
But the researchers identified 29 women with the AIDS virus who also had an HPV infection, cleared it and had it come back -- even though the women had been celibate for 18 months or more.
This fits "a stringently defined pattern highly consistent with HPV reactivation," the researchers wrote in their report, published in this week's issue of the Journal of the National Cancer Institute.
"That is, an initially detected HPV type was subsequently not detected for at least two sequential visits and then was detected a second time, in a subject who had remained sexually inactive from the time the HPV type became undetectable and then detectable again (minimizing the possibility of new sexual transmission)."
Dr. Howard Strickler of Albert Einstein College of Medicine in New York and colleagues at eight other institutions said their findings suggest that women with HIV and perhaps other women with suppressed immune systems, such as transplant and cancer patients, need to have regular Pap smears.
Cervical cancer is easily cured if caught early but is deadly in later stages.
"Our data suggest that undetectable HPV infections become active much more frequently in HIV-positive women, which helps explain the extremely high rates of HPV infection in these women," Strickler said in a statement.
The study supported the idea that HPV is transmitted sexually. Women were much more likely to be infected with HPV after a recent sexual encounter.
"Even one male sexual partner among married women (presumably a monogamous relationship with the subject's husband) was associated with risk of incident HPV detection," the researchers wrote.
SAN FRANCISCO (AFX) -- Gilead Sciences Inc. said after Tuesday's closing bell that it is proceeding with the evaluation of a second formulation of a fixed-dose combination of Truvada and Bristol-Myers Squibb's Sustiva for the treatment of HIV. If the second formulation is proven to be bioequivalent to the products dosed simultaneously as separate pills, the companies could submit a new drug application requesting marketing approval of the fixed-dose combination to the Food and Drug Administration before the end of 2005.