News (Updated September 21, 2003)

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Merck, Aventis Begin Trials of Combo AIDS Vaccine

Wed Sep 17, 4:27 PM ET

NEW YORK (Reuters) - Drug makers Merck & Co. and Aventis said on Wednesday they have begun human clinical trials of a novel combination AIDS vaccine.

The trials seek to determine whether the addition of a vaccine made by Aventis to Merck's vaccine candidate will prove more effective than either alone.

The creation of an AIDS vaccine represents the Holy Grail of AIDS research. Current treatments lessen symptoms or delay progress of the disease but do not prevent or cure it.

Earlier this year the most advanced AIDS vaccine clinical trial, by Vaxgen Inc., reduced the rate of HIV infection by just 3.8 percent in 5,400 men and women considered at high risk.

At least 30 other AIDS vaccines are in various stages of development.

Merck first began testing its HIV vaccines in humans in late 1999. The company's current candidate, known as the replication-defective adenovirus type 5 vector, is based on a modified common cold virus which is used to deliver an HIV gene into cells to produce a strong immune response to HIV.

Aventis's Alvac HIV vaccine has been in development since 1992. It is a canarypox vector which is used to deliver HIV genes into cells.

 

Effective Methadone Dose Does Not Harm Newborns

Wed Sep 17, 3:12 PM ET

By Karla Gale

NEW YORK (Reuters Health) - Treating heroin-addicted pregnant women with the most effective dose of methadone does not increase their infants' symptoms of withdrawal after they are born, new study findings suggest.

Instead, methadone appears to reduce risks to both mother and infant by preventing illicit drug use.

Methadone is often substituted for heroin and other opiates when patients are treated for their addiction. When the methadone dose is high enough, it blocks the effects of heroin and reduces addicts' craving for the drug.

Many physicians believe that methadone doses should be kept no higher than 20 milligrams per day when women are pregnant, lead investigator Dr. Vincenzo Berghella told Reuters Health. But effective doses for pregnant women range from 50 to 200 mg daily.

Therefore, his research group, based at Jefferson Medical College of Thomas Jefferson University in Philadelphia, examined the records of 100 mother-newborn pairs treated in their comprehensive program for drug-addicted pregnant women. Methadone doses ranged from 20 to 200 mg per day, they note in their article in the American Journal of Obstetrics and Gynecology.

Their study differed from previous research, they point out, because it examines higher average doses and the last dose prior to delivery. They also scored the newborns' withdrawal problems using an objective measure of clinical signs and symptoms, called the Newborn Abstinence Score (NAS).

Birth weight, highest NAS, presence of neonatal withdrawal, and average duration of treatment for withdrawal did not differ significantly between the higher doses and lower doses of methadone.

"I was happily surprised when our data confirmed that using an effective dose is best for both the women and their babies," Berghella said.

He added that prior research demonstrated that methadone has no long-term effects on the fetus, "just short-term withdrawal," which occurred in 60 percent of the babies.

"Effective maintenance prevents drug hunger and craving and blocks the euphoric effect of illicit drugs," he noted. As a result, the fetus is not exposed to erratic maternal opioid levels, protecting it from repeated episodes of withdrawal.

Furthermore, he said, "by preventing drug-seeking behavior, women are less likely to engage in prostitution or other behaviors that increase their risk of HIV, hepatitis infection, and other sexually transmitted diseases."

He advises heroin-addicted women to check into a program that not only helps them with their symptoms of withdrawal, but also addresses psychological and social issues. The program at Jefferson Medical College "even helps women find housing, stay away from an abusive partner, and provides basic preventive medical care.

"That way, people can become clean and can stay clean," Berghella concluded.

SOURCE: American Journal of Obstetrics and Gynecology, August 2003.

 

New Treatment May Flush Out Hidden AIDS Virus

Wed Sep 17, 8:34 AM ET

By Maggie Fox, Health and Science Correspondent

WASHINGTON (Reuters) - A two-step approach against AIDS involving first flushing the virus out of hiding then killing it with a toxic antibody may offer the first hope for controlling a lifelong AIDS infection, U.S. researchers reported on Tuesday.

The technique to locate and kill dormant HIV-infected immune system cells works in mice and is ready to test in monkeys, the team at the University of California, Los Angeles, said.

It would not offer a cure, but might be a way to help people eventually stop taking the powerful drug cocktails that can keep the virus at bay, but which cause serious side-effects from diarrhea to heart disease.

"Our findings show potential for flushing HIV out of its hiding places in the body," Dr. Jerome Zack, an associate director of basic sciences for the UCLA AIDS Institute, said in a statement.

Highly active antiretroviral therapy, or HAART, can keep HIV patients healthy for decades, but they do not reach a latent virus -- which has been found to lurk inside immune system cells for decades and probably for a lifetime.

Writing in the September issue of the journal Immunity, Zack and colleagues said they had devised a two-step system for first partially activating the cells the virus hides in, then killing the cells before the virus can escape.

The cells they targeted are called resting T-cells. T-cells are the immune system cells that HIV likes best to infect, and these cells can go dormant for long periods of time.

When they are dormant, HIV drugs cannot find them and work against the virus hiding inside.

"About one in a million T-cells holds latent HIV that the antiretroviral drugs can't touch," said Zack. "In order to make it visible, so you can attack it, you have to activate it," he added in a telephone interview.

Attempts to do so have failed in the past because activating all of a patient's T-cells can create potentially deadly illness.

TOXIN KILLS INFECTED CELLS

Zack's team used two compounds to only partially activate the T-cells.

One, interleukin-7 or IL-7, is a naturally occurring compound. The other, called prostratin, comes from a tree native to the Pacific island of Samoa.

"They hit a specific activation pathway but don't fully turn on cells," Zack said.

At that point they fire the "guided missile" -- an antibody, or targeting immune system compound, spliced to a piece of diphtheria toxin.

"Because the antibody is linked to a toxin molecule, it pops into the cell," Zack said. "The toxin kills the cell before lots of viruses are made."

The approach worked in mice, clearing 70 percent to 80 percent of the reservoir of latent T-cells, Zack said. It did not mistakenly attack healthy cells -- an important finding.

But HIV is difficult to experiment with in animals because it is a virus that affects humans in a unique way. Zack said the next step is to try it in monkeys infected with an engineered human-monkey virus called SHIV.

If tested in people, Zack envisions it would be used along with a HAART cocktail to keep HIV from spreading any further in the body.

Even then, he does not think it would offer a complete cure. HIV is believed to hide in other reservoirs, including certain brain cells. It can reactivate if HAART is stopped -- but patients may be able to safely stop HAART for years or even decades.

AIDS has killed 28 million people worldwide since the epidemic began in the 1980s, most of them in Africa, where drugs that can fight the disease are a rare luxury.

 

PET Scans Used to Detect HIV Progression

Thu Sep 18, 7:06 PM ET

By Patricia Reaney

LONDON (Reuters) - A scanning technique can track the progression of HIV and could lead to new treatment options and the development of the next generation of anti-AIDS drugs, scientists said on Friday.

Positron emission tomography (PET) scans are usually used to identify cancerous tumors, but researchers in the United States believe the technology could play an important role in the battle against AIDS by identifying the impact of the virus on lymph nodes which could be treated with radiotherapy or surgery.

Dr C. David Pauza and scientists at the University of Maryland Biotechnology Institute in Baltimore Maryland took whole body PET scans of 15 HIV patients and found fairly distinct sites of immune response during different stages of the illness.

"We believe that if we identify those sites clearly during HIV infection we encourage people to consider these types of interventions," Pauza said in an interview, referring to surgery or radiotherapy.

During early disease, lymph nodes in the head and neck were activated, according to the PET scans, but in later stages the virus stimulated an immune response in areas of the torso and later in the bowel.

HIV/AIDS is treated with antiretroviral drugs. Surgery or radiotherapy would open up a new approach to the illness that has affected 42 million people worldwide.

"We are not aware that it has ever been tried," said Pauza, who reported his findings in The Lancet medical journal.

"We think it is appropriate to consider these approaches and also appropriate to learn from the cancer models because cancer is a disease of chronic cell activation and growth and in some ways, even though HIV is triggered by a virus, it has some similarities," he added.

In cancer patients, PET scans measure the activity of cancerous cells, while in HIV it picks up levels of immune system reaction.

David Schwartz and Sujatha Iyengar, of the Johns Hopkins University Bloomberg School of Hygiene and Public Health who also used PET scans to track HIV progression, said lymph node removal could give patients an opportunity for a break in antiretroviral treatment.

"Although many systemic sites from which latent virus could be re-activated would be left, re-activation might not occur for months or years after removal of the active nodes, thereby allowing extended interruption of treatment," Schwartz said in a separate study published in The Lancet.

Pauza also suggested that with the pattern of progression detected with the PET scans it could be possible to develop a prognostic tool for HIV, new drugs for patients in whom existing therapies have failed, or other illnesses.

One thing we discovered as we were going through this work is that there was a substantial amount of undiagnosed cancer associated with HIV. We observed a number of patients with lymphoma," he added.

 

Understanding AIDS stigmas key to breaking them, say researchers

Fri Sep 19, 1:38 AM ET

GABORONE (AFP) - The stigma surrounding AIDS remains a major barrier to treatment in southern Africa, but in Botswana, 31-year-old Kgalelo Ntsete dazzled about 3,000 spectators when she won a beauty competition for the HIV-positive earlier this month.

That was an effort in the world's worst-affected country, where almost 40 percent of adults are infected and life expectancy has plunged from 67 to 42, to bring AIDS out of the closet.

Former South African president Nelson Mandela told recently how villagers had shunned him after he visited a house where two boys had died of AIDS.

"As we were going through this house the people of the village were singing freedom songs and I went inside," he told a television interviewer.

"When I came out I go to join them... they had moved away -- the stigma.

"Then I decided to walk fast to make sure that they were moving away from me and when I walked faster they also walked faster away -- the stigma."

Mandela said that another time he took Britain's late Princess Diana to see AIDS sufferers.

She "shook hands with them, sat down at their bed," he said.

"Now the people felt that if a British princess could come to a hospital with AIDS sufferers and nothing happens to her, then there (it) is nothing but superstition. Just superstition."

Mandela also revealed recently that one of his nieces and two great-nephews had died of AIDS to show that it can happen in the best of families -- but the parents refused to let him identify them.

"Many people are calling urgently for laws and policies to curtail HIV/AIDS stigmas," South African AIDS researchers David Patient and Neil Orr said in an article.

"But it is a useless exercise until such time as we examine the roots of the stigma and understand its very nature."

"It is believed that the person is going to get sick at home at some point, which means that scarce resources are going to be used, with no cure or recovery to justify the investment of those resources.

"Just like any other apparently irrational behaviour, at the core of stigma is a set of beliefs, presented as facts, that is creating discriminatory behaviour."

Hellen Ditsebe, 44, the first woman in Botswana to go public about her status, told AFP Wednesday that she was banned from the family home and barred from using the family surname after she revealed in 1992 that she was HIV-positive.

"My family and the community could not accept it," she said.

"I had to move out because no one wanted me."

The mother of three, who has recently decided to adopt five orphans, is often seen around shopping centres urging people to use condoms.

She has gained courage -- and weight --- after being enrolled in an anti- retroviral therapy programme.

"I do not think (the stigma) will disappear easily," she said.

"Recently, I attended an AIDS workshop and one woman refused to share a toilet with me."

Vuyani Jacobs, 32, who lives in the Khayelitsha township outside Cape Town and has been HIV positive for 11 years, says the key to breaking the stigma is to be open about the disease.

"When people first found out that I was HIV-positive they didn't seem to know whether to hug me or cry or say 'hello'. It was uncomfortable, so for a long time I isolated myself because I was scared that people would reject me," said the labour consultant for the AIDS activist group Treatment Action Campaign.

"But today I go to shebeens (bars), drink a beer and play pool. I've found that the more you engage with people and talk about your disease, the less they shut you out."

Warren Parker, the head of South Africa's Centre for AIDS Development and Research, says African countries are at different stages of the disease, which means the problem of stigmatisation is at different levels across the continent.

"At the beginning of an epidemic it is fairly normal for people to discriminate and stigmatise, because they have a psychological fear of the disease being transmitted," he says.

"But as the disease progresses, more people come into contact with people who have fallen sick, and they begin to understand it a lot better."

 

Cheaper for S. Africa Firms to Treat HIV -Expert

Tue Sep 16,10:32 AM ET

JOHANNESBURG (Reuters) - South African companies would be better off treating employees with the HIV virus than to ignore the illness, which affects at least 11 percent of the population, a doctor at a top insurance broker said on Tuesday.

Dr. Grietjie Strydom -- who set up the health unit at financial services group Alexander Forbes -- said it would be much cheaper for local firms to provide employees who have the virus with antiretroviral drugs than to do nothing.

"It is economically viable to treat a single HIV positive employee. It costs less than to do nothing," she told reporters.

South Africa has more people with HIV or AIDS than any other country in the world. President Thabo Mbeki's government recently bowed to pressure and plans to start distributing anti-retroviral drugs by the end of the year.

Prior to the decision, the government had opposed the drugs on grounds of cost, side-effects and the lack of health infrastructure.

Mining companies -- which are believed to have the highest HIV prevalence rate -- have taken the lead in providing comprehensive treatment programs to employees.

Strydom said a company with 635 employees and an 11 percent HIV infection rate would save a total of 3.75 million rand ($500 million) with a full treatment program, including drugs, counselling and HIV disability insurance.

An untreated employee would cost the company 55 additional days of sick leave in the final two years of his or her life, along with a 25 percent fall in productivity over that period.

There would also be the cost of recruiting and training a replacement when the employee finally stopped working.

An HIV positive employee treated for the disease would work productively for another seven years, while insurance companies would cover the disability cost of the final two years of his or her life if the package was negotiated properly, she said.

"It's a win-win situation for everybody," she said, speaking at a media seminar by top executives from the firm. Alexander Forbes is one of the world's top 10 insurance brokers, with asset management, risk and advisory services.

Strydom said that some white-collar companies believed that if they had a low HIV-AIDS prevalence rate, they didn't need a full treatment program.

This was a mistake because if a company which paid high salaries had a three percent prevalence rate the disease would cost them as much as a company which paid low salaries, but had a 30 percent prevalence rate, she said.


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