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August 17, 2008)
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Wed, Aug 13 02:35 AM
By Maggie Fox, Health and Science Editor
WASHINGTON (Reuters) - A woman who has never shown symptoms of infection with the AIDS virus may hold the secret to defeating the virus, U.S. researchers said on Tuesday.
Infected at least 10 years ago by her husband, the woman is able somehow to naturally control the deadly and incurable virus -- even though her husband must take cocktails of strong HIV drugs to control his.
She is a so-called "elite suppressor," and studies of her immune cells have begun to offer clues to how her body does it, the team at Johns Hopkins University in Baltimore said.
"This is the best evidence to date that elite suppressors can have fully pathogenic virus," said Dr. Joel Blankson, who led the study.
"The feeling was initially that they had defective virus," Blankson added in a telephone interview.
But the couple has been monogamous for at least 17 years, Blankson said, and tests show they are infected with the same strain of virus. What is different is the immune system of the wife, who cannot be named for privacy reasons.
"That's a good sign in terms of developing a therapeutic vaccine," Blankson said. Such a vaccine would not prevent infection but might be used to treat patients.
The AIDS virus infects at least 33 million people globally and more than a million in the United States. It has killed 25 million people since it was identified in the early 1980s.
New figures show 56,000 people are infected every year in the United states, mostly gay and bisexual men but also injecting drug users and their sexual partners, both male and female, as well as newborns and recipients of contaminated blood transfusions.
STALLING REPLICATION
Both the man and the woman, who are from Baltimore, were diagnosed 10 years ago, Blankson said. The husband is a former injecting drug user.
Tests showed that immune cells known as CD8 T-cells from the wife stalled HIV replication by as much as 90 percent, while the husband's T-cells stopped it by only 30 percent, Blankson's team reported in the Journal of Virology.
Her virus has also mutated in apparent response to this immune attack, becoming weaker, while her husband's virus has remained strong.
"Elite suppression offers clues to vaccine researchers on many fronts: how CD8 killer T-cells can attack HIV and how a stronger immune response can force HIV into a permanent defensive state," Blankson said.
"We are trying to figure out exactly how the T-cells work in her to inhibit viral replication," he added. "We are just trying to see what kind of cytokines they make."
Cytokines are immune system signaling proteins. One thing the researchers have noticed is that while the husband's T-cells make just one, called gamma interferon, hers made both that one and another called TNF, or tumor necrosis factor.
That cannot be the whole story, though, because AIDS researchers have tried using such immune system proteins in patients and they did not work well.
And her immune cells seem to make the response only when they encounter the virus.
Another clue: the woman may have unusual activity in her human leukocyte antigen system, or HLA, Blankson said. This important component of the immune system helps recognize antigens -- protein identifiers -- of enemies such as bacteria and viruses.
Mon Aug 11, 2008 8:00 PM BST
By C. Vidya Shankar, MD
MEXICO CITY (Reuters Health) - Long-term treatment of genital herpes with the drug acyclovir does not reduce the rate of new HIV infections, researchers reported at the International AIDS Conference here last week.
They said the findings are surprising, because prior infection with herpes simplex virus type 2 (HSV-2), the virus that causes genital herpes, has been reported to increase the risk of HIV many fold.
In a randomized multicenter trial, Dr. C. Celum of the University of Washington, Seattle, and colleagues evaluated the effects of acyclovir in 1,814 gay men who have sex with men from the United States and Peru, and in 1,358 women from Zimbabwe, Zambia and South Africa. All were infected with HSV-2 but not with HIV, the virus that causes AIDS.
Subjects took acyclovir or placebo pills twice daily and were followed monthly for up to 18 months.
While the incidence of genital ulcers was significantly lower in the acyclovir group, the incidence of HIV infection was the same in both the groups, the researchers observed.
They suggest that infection with the genital herpes virus may be a risk marker, not a risk factor, for HIV infection. Alternatively, perhaps, the interventions against HSV were not potent enough.
BOSTON (Reuters) - Married women in India who are physically and sexually abused by their husbands are four times more likely to become infected with the AIDS virus than married women who were not abused, a Harvard study said on Tuesday.
India has the world's third-largest number of people infected with HIV at 2.47 million cases, according to the latest figures, but health workers say the number is rising rapidly and spreading to new population groups.
Researchers at the Harvard School of Public Health said they confirmed earlier studies suggesting that men who engage in extramarital sex, including unprotected sex with prostitutes, are the main source of HIV for Indian women.
More than 95 percent of HIV-positive married Indian women report being monogamous, the Harvard researchers said, adding that the extramarital sex by their husbands explains why so many victims of abuse are becoming infected.
"A women who is abused by her husband is truly placed in a situation of 'double jeopardy' regarding HIV infection," said Jay Silverman, lead author of the study published in the Journal of the American Medical Association.
"His sexual behavior outside of the marriage makes it more likely he is infected with the virus, and his abusive behavior inside the marriage leaves her with little control over sex or sexual protection," said Silverman, an associate professor at the Harvard School of Public Health.
The study examined data from India's National Family Health Survey between 2005 and 2006, with a sample that included 28,139 married women.
More than a third reported experiencing physical violence with or without sexual violence from their husbands. Of these, 28 percent experienced physical violence alone, while 7.7 percent suffered both physical and sexual abuse.
The risk for HIV infection among those who experienced both physical and sexual violence from their husbands was increased by a magnitude 3.9 over the infection risk for women who were not abused, the researchers said.
(Reporting by Jason Szep, editing by Philip Barbara)
Monday August 11, 9:12 pm ET
By Marcus Wohlsen, Associated Press Writer
Gilead announced that the Food and Drug Administration is joining regulators in Europe, Turkey, Australia and New Zealand by allowing the company to market Viread as a tool for suppressing the chronic liver disease.
Sales of Viread as a stand-alone pill have declined in recent years following Gilead's launch of Truvada and Atripla, which combine Viread with other drugs and currently dominate the market.
Viread debuted in 2001 and quickly became a top-selling anti-HIV treatment. Sales peaked at nearly $783 million in 2004 before Gilead's own competing drugs began chipping away at Viread's share of the AIDS drug market.
Viread had about $613 million in sales last year on total company revenues of $3.73 billion.
Wall Street analysts anticipating Viread's approval Monday have called the market for hepatitis B drugs significant, since only a small fraction of more than 1 million in the U.S. estimated to be infected with the virus have been diagnosed.
The Foster City-based company sells another hepatitis B treatment, Hepsera, which reported sales of $303 million last year.
The FDA's approval was based on two clinical trials that showed Viread was more effective than Hepsera at combatting liver inflammation and scarring caused by hepatitis B, the company said.
The infectious disease is blamed as a major cause of liver cancer and is especially common in the U.S. among Asian-Americans owing to the prevalence of hepatitis in Asian countries.
Also Monday, the 9th U.S. Circuit Court of Appeals in San Francisco reinstated a lawsuit against Gilead claiming the company cost shareholders money by allegedly marketing Viread for unapproved or "off-label" uses.
The appeals court reversed a lower court's decision dismissing the suit filed by disgruntled shareholders in November 2003. Gilead declined to comment on the court's decision Monday.
By Will Dunham
WASHINGTON (Reuters) - A drug that Novartis AG is testing in people with multiple sclerosis also has the potential to treat certain viral infections, perhaps including the AIDS virus, U.S. researchers said on Wednesday.
Low doses of the drug FTY720, also called fingolimod, given to mice once a day for three days eliminated an infection by a virus that can cause meningitis, an inflammation of the membranes surrounding the brain and spinal cord.
The findings suggest the drug, which boosted anti-viral immune responses in the mice, may be useful against viruses that cause high-level, long-lasting infections in people such as hepatitis C and HIV, the researchers said.
Microbiologist and immunologist John Altman of Emory University in Atlanta, who led the study, said the researchers plan to assess the effects of the drug on other viruses including the monkey version of the AIDS virus.
Altman, whose findings were published in the journal Nature, expressed cautious optimism that the drug might work against certain chronic viral infections in people.
"We think it's crucial that we do experiments to check it out," Altman said in a telephone interview.
The drug is generally considered to be an immunosuppressant that works to restrain the body's natural defenses.
That could be helpful in multiple sclerosis, an autoimmune disease in which the immune system attacks body parts as if they were foreign invaders.
But one effect of the drug seems to facilitate the immune response, the researchers said. FTY720 among other things traps white blood cells -- key soldiers in the immune system's fight against infections -- in the lymph nodes, Altman said.
With viral infections, the lymph nodes are where the immune response can get primed and started, Altman said. Some viruses replicate themselves at high levels in lymph nodes, including the human immunodeficiency virus that causes AIDS.
They tested the drug against a mouse virus called lymphocytic choriomeningitis, which causes chronic infections by escaping immune responses.
"In the absence of treatment (with FTY720) we have an exhausted immune response. In the presence of treatment, we regain a robust cellular immune response," Altman said.
Swiss drug maker Novartis said in June two multiple sclerosis patients taking FTY720 in clinical trials had problems with infections and one died, but the role of the drug in the cases was unclear.
Novartis plans at the end of 2009 to seek approval by the European Union for FTY720 to treat MS, spokeswoman Valerie Tate said by e-mail. The drug is currently in late-stage trials.
Altman said his study was backed by the U.S. government's National Institutes of Health and was not funded by Novartis.