By Karla Gale

NEW YORK (Reuters Health) - The Global HIV/AIDS Vaccine Enterprise, an international alliance of independent organizations supporting HIV vaccine research, has issued a roadmap to speed the development of a vaccine by promoting new collaboration, resources, and strategic focus.

"Harnessing new scientific opportunities for HIV vaccine development will require an effort of a magnitude, intensity, and design without precedent in biomedical research," the coordinating committee of the Enterprise writes in the Public Library of Science-Medicine.

"The first trial of an HIV vaccine was done almost 18 years ago. We have come to realize that developing an HIV vaccine is much more complex than we all thought," Dr. Jose Esparza, of the Bill and Melinda Gates Foundation, told Reuters Health.

To make an HIV vaccine a reality in the foreseeable future, "we need a new game plan that brings more corroboration, a better exchange of information and a more systematic approach to explore different vaccines," he said.

The committee hopes to "develop a common set of criteria to make decisions about which ones should be tested and which ones should move to larger scale trials," he added. "The field today is inundated with 'me-too" products, similar candidate vaccines, and not enough innovation."

The scientists were able to agree on the scientific questions that must be answered to develop an HIV vaccine that induces both cellular and antibody immunity, Esparza said. But without the Enterprise, "the current system does not have the required infrastructure or resources to answer those questions."

Specific goals will be to develop new standard assays, a system of "core" reference laboratories that will service satellite labs; a global quality assurance function to encompass all participating laboratories; and a source of common lab materials.

The Enterprise Coordinating Committee estimates that, to meet these goals, current expenditures on HIV vaccine research and development will need to be doubled to $1.2 billion annually.

This proposal is "an excellent start to a continuing dialogue of utmost importance," Dr. David D. Ho, the director of the Aaron Diamond AIDS Research Center in New York, comments in a related editorial.

SOURCE: Public Library of Science-Medicine, February 2005.

© Reuters 2005. All Rights Reserved.

WASHINGTON (Reuters) - A "morning after" treatment for the AIDS virus can help prevent infection after a rape, contact with a contaminated needle or even a night of passion without a condom, U.S. health officials said on Thursday.

Taking drug cocktails for four weeks seems to greatly reduce the risk of becoming infected with the virus, which is transmitted through sex -- heterosexual and homosexual -- drug use and shared needles, the Centers for Disease Control and Prevention said.

These drug cocktails, called highly active antiretroviral therapy or HAART, are routinely taken for life by HIV-infected patients who can afford it and have access. HAART can keep a patient healthy despite infection with the deadly and incurable virus.

The CDC said there was no ethical way to do a random trial comparing post-exposure prevention to a placebo or dummy pill.

But trials on animals and studies of rape victims and of people at high risk of HIV infection because of their behavior have shown that taking a two- or three-drug cocktail after the possible exposure does prevent infection.

"A 28-day course of HAART is recommended for persons who have had nonoccupational exposure to blood, genital secretions, or other potentially infected body fluids of a person known to be HIV infected when that exposure represents a substantial risk for HIV transmission," the CDC said.

The quicker, the better, it said.

In its report, the CDC pointed to a study of needlestick injuries to health-care workers. "In this study, the prompt initiation of zidovudine (AZT) was associated with an 81 percent decrease in the risk for acquiring HIV."

In another trial of 200 gay and bisexual Brazilians at high risk of HIV infection, doctors gave out "starter packs" of AZT and another AIDS drug called lamivudine.

In the group that used the drugs after having unprotected sex, one person became infected, while 11 people in the group that did not take the drugs became infected.

South African rape victims got a similar treatment and none of the women who started the drugs within 48 to 72 hours became infected.

"Although 400,000 new HIV infections occur in the United States each year, relatively few exposed persons seek care after nonoccupational exposure," the CDC said.

"Preferred regimens include efavirenz and lamivudine or emtricitabine with zidovudine or tenofovir and lopinavir/ritonavir (coformulated in one tablet as Kaletra) and zidovudine with either lamivudine or emtricitabine. Different alternative regimens are possible."

© Reuters 2005. All Rights Reserved.

U.S. Warns of Safety Risks of Boehringer AIDS Drug

Wed Jan 19, 2005 06:18 PM ET

By Lisa Richwine

WASHINGTON (Reuters) - An important AIDS drug can cause sometimes deadly liver damage but remains a key option for many patients, U.S. health officials warned on Wednesday.

The Food and Drug Administration said doctors should weigh benefits and risks before prescribing the drug, Boehringer Ingelheim's Viramune, also known by the generic name nevirapine.

No serious liver toxicity or deaths have been reported when a single dose was given to prevent mother-to-child transmission of the deadly HIV virus that causes AIDS, the FDA said.

Nevirapine is distributed for that use in African countries as part of President Bush's effort to fight the spread of AIDS. The drug is also used in the United States.

Controversy has swirled recently in Africa, with South Africa's ruling African National Congress accusing U.S. officials of conspiring with Boehringer Ingelheim, a private company based in Germany, to hide nevirapine's side effects. U.S. health officials dispute the charge.

The FDA, in a statement, said cases of liver damage that produce a rash, fever or other symptoms were more common with nevirapine than with other HIV-fighting drugs. Some instances have been fatal, including some in pregnant women.

Females and patients with higher counts of infection-fighting cells called CD4 cells have greater risks of developing liver damage, the FDA said.

The FDA said side-effect warnings had recently been revised on the drug's prescribing information.

Nevirapine is one of the medicines used in drug cocktails that can suppress the HIV virus and keep patients healthy. HIV patients have limited options for suppressing the fatal virus, and alternative drugs also have serious side effects, the agency said.

"In spite of the potential for serious and life-threatening liver toxicity and skin rashes with nevirapine, there are multiple reasons why nevirapine remains an important part of an HIV treatment regimen (for many people)," the FDA said in a statement.

A Boehringer spokeswoman could not immediately be reached for comment on Wednesday.

The AIDS virus killed 2.3 million people in Africa in 2004.

Nevirapine came under question recently when a scientist from the National Institutes of Health, who was fired but is contesting the dismissal, charged a study of the drug in Uganda was sloppily run.

A committee of experts at the Institute of Medicine is reviewing the research to see if it was so flawed the data are useless.

The NIH has said the allegations are false and endanger the lives of babies because people will be afraid to use a valuable drug.

GENEVA, Jan 20 (Reuters) - The World Health Organisation (WHO) said it would continue recommending use of the Viramune drug in AIDS patients despite a U.S. regulatory warning, as the benefits were greater than toxicity problems.

"We don't think at the moment to change our policy ...," Charles Gilks, director of WHO's AIDS treatment and prevention scale-up team, told Reuters on Thursday.

"We are aware of the toxicity profile, but at the moment we believe the benefits outweigh any problems," he said.

All anti-retrovirals are toxic to some extent and require monitoring, according to the WHO expert.

Germany's Boehringer Ingelheim said on Thursday that it expected no impact on its AIDS drug-donation programme for poor countries from a warning by the U.S. Food and Drug Administration (FDA) that its Viramune medicine, whose generic name is nevirapine, could cause liver damage.

The WHO, a United Nations agency, especially recommends the use of nevirapine in AIDS patients with significantly weakened immunity systems, as well as in pregnant women who carry the deadly HIV virus, according to Gilks.

"It has a major use in preventing mother-to-child transmission. There is no evidence that for short periods of time this toxicity occurs in pregnant women. It takes several weeks to build up," he said.

Gilks added: "It is reassuring that there is no evidence that there is any problem in children."

Nevirapine is one of the medicines used in a drug cocktail that can suppress the HIV virus and keep patients healthier longer.

Daniel Berman, coordinator of MSF's Campaign for Access to Essential Medicines, said of the FDA advisory: "This is a formalisation of something known in the medical community.

"All of the drugs have side effects and should be monitored at the beginning of treatment. Other drugs have other issues, none of them is perfect."

Fernando Pascual, a pharmacist working on MSF's campaign, said that the risks associated with Viramune were well-known and came in the first weeks of treatment.

"We use it in our projects and pay special attention to liver toxicity and are ready to switch to other treatments in case we detect toxicity," he told Reuters.

He named the generic efavirenz, which is marketed in the United States, Canada and some European countries by Bristol-Myers <BMY.N> as Sustiva, and elsewhere by Merck <MRK.N> as Stocrin.

By Sitaraman Shankar and James Macharia

FRANKFURT/JOHANNESBURG, Jan 20 (Reuters) - Germany's Boehringer Ingelheim expects no impact on its AIDS drug donation programme for poor countries from a U.S. regulatory warning that its Viramune medicine could cause liver damage, it said on Thursday.

A spokeswoman for privately owned Boehringer, Germany's top drugmaker by sales, said there would be no change in its policy of offering Viramune free of charge to developing countries for prevention of mother-to-child transmission of HIV.

Health officials and activists fighting the AIDS disease in South Africa also stood by Viramune, though the ruling African National Congress (ANC) said the FDA warning vindicated its concerns about the drug.

The U.S. Food and Drug Administration (FDA) warned on Wednesday that doctors should weigh benefits and risks before prescribing Viramune, which was linked with some deaths, including in pregnant women. Viramune is also called nevirapine.

Offered free for preventing mother-to-child transmission, Viramune is also part of a subsidised anti-AIDS cocktail used as a continuous therapy that also features Bristol-Myers Squibb's <BMY.N> stavudine and GlaxoSmithKline's <GSK.L> lamivudine.

"There is no consequence for our donation or for supply of the drug for continuous treatment at reduced prices in developing countries," the Boehringer spokeswoman said.

"We do not expect any major effects on the behaviour of doctors or on our sales as a result of the FDA warning."

She said the company was in discussions with the European regulatory body EMEA over consequences of the FDA's warning on its labelling in Europe.

The controversy is a particularly sensitive subject in South Africa, which has the world's highest caseload of HIV and AIDS with some 5 million people infected out of a population of 45 million. Activists reckon 600 patients die there daily.

"Any fundamental change in the policy (to use nevirapine) will be determined by compelling evidence scientifically supported by the World Health Organisation," said Solly Mabotha, spokesman of the South African department of health. The department oversees the country's anti-retroviral (ARV) treatment programme.

South Africa's ruling ANC sparked a controversy recently last month by accusing U.S. officials of conspiring with Boehringer to hide the side effects of nevirapine. U.S. health officials disputed the charge.

"Our position is the same, that ARVs have serious side effects and the FDA is confirming that," ANC's head of the presidency and communications, Smuts Ngonyama said.

Activists said they had little choice for now.

"Unfortunately we don't have a choice. As consumers we cannot say we're going to stop, until the body that controls nevirapine in the country says so, by which time there may be a better alternative," said Thanduxolo Doro, a spokesman for South Africa's National Association of People with AIDS (NAPWA).

LIVER DAMAGE

The FDA said cases of liver damage that produce a rash, fever or other symptoms were more common with nevirapine than with other HIV-fighting drugs.

But no serious liver toxicity or deaths had been reported when a single dose was given to prevent mother-to-child transmission of the HIV virus.

Viramune had sales of 310 million euros ($402.6 million) in 2003, making it Boehringer's sixth-biggest drug.

"Doctors treating HIV patients with the AIDS cocktail including nevirapine need to carefully monitor patients in the first 46 weeks because of potential liver toxicity," the Boehringer spokeswoman said.

The FDA said side-effect warnings had recently been revised in the drug's prescribing information.

Zackie Achmat, head of South Africa's leading AIDS lobby the Treatment Action Campaign, who is himself on antiretroviral treatment, said the FDA's findings were not new and that all ARVs were known to have side-effects including liver damage.

By James Macharia

JOHANNESBURG, Jan 20 (Reuters) - Health officials and activists fighting AIDS in South Africa on Thursday stood by a key drug the U.S. Food and Drug Administration (FDA) warned a day earlier could cause deadly liver damage.

But the ruling African National Congress (ANC) said the FDA warning vindicated its concerns about the drug. In December, it accused U.S. health officials of conspiring with German drug firm Boehringer Ingelheim to hide adverse affects.

The FDA warning is particularly sensitive in South Africa, which has the world's highest caseload of HIV and AIDS with some 5 million people infected out of a population of 45 million. Activists reckon 600 people die daily from HIV/AIDS.

"Any fundamental change in the policy (to use nevirapine) will be determined by compelling evidence scientifically supported by the WHO (World Health Organisation)," said Solly Mabotha, spokesman at the Department of Health, which oversees the anti-retroviral (ARV) treatment programme.

He said the department was working with research institutions to fully understand nevirapine's adverse effects.

NO CHOICE

Nevirapine is the generic name for Viramune, made by Boehringer, and is distributed across Africa as part of U.S. President George W. Bush's effort to fight the spread of AIDS.

It is one of the medicines used in drug cocktails that can suppress the HIV virus and keep patients healthy longer.

In December, the ANC accused U.S. officials of conspiring with Boehringer "to tell lies" about the safety of nevirapine to promote sales in Africa. U.S. health officials disputed the charge.

"Our position is the same, that ARVs have serious side-effects and the FDA is confirming that. We still stand by our statement issued last month (about the conspiracy)," ANC's Head of the Presidency and Communications, Smuts Ngonyama said.

In its warning issued on Wednesday, the FDA asked doctors to weigh benefits and risks before prescribing nevirapine.

Boehringer said the FDA warning would not stop it from offering Viramune free of charge to prevent mother-to-child transmission of HIV in poor countries.

"Doctors specialising in HIV were aware of liver toxicity issues and we do not expect any major change in treatment including nevirapine," a company spokeswoman said.

Activists said they had little choice for now.

"As consumers we cannot say we are going to stop until the body that controls nevirapine in the country says so, by which time there may be a better alternative," said Thanduxolo Doro, a spokesman for South Africa's National Association of People with AIDS (NAPWA).

Zackie Achmat, who heads South Africa's leading AIDS lobby, the Treatment Action Campaign, and is himself on antiretroviral treatment, said the FDA's findings were not new. All ARVs were known to have side-effects, including liver damage, he said.

India to undergo human trials for HIV vaccine in Feb

NEW DELHI (AFX) - Human trials of a vaccine to focus on the sub-type C of the HIV virus are set to begin in India next month, at the National AIDS Research Institute in Pune, west of Bombay, said US infectious disease specialist Seth Berkley.

Epidemiologist Berkley founded the New York-based International Aids Vaccine Initiative (IAVI) in 1996 and says a vaccine is the only way to stop what he calls the 'greatest plague since the 14th century.'

He has been in New Delhi meeting with officials to discuss the spread of AIDS in India, which has 5.1 mln HIV-infected people - the second most in the world after South Africa.

Besides the planned trials in India, others are underway against different virus strains in the US, Europe, Africa and South America.

The sub-type C of the virus is the most common in the Asian nation.

The quest for a vaccine is particularly crucial in India, where the World Bank has warned that the disease is on tract to become the single largest cause of death in the nation of more than 1 bln people by 2033.

Around 38 mln people worldwide are living with HIV, according to UNAIDS.

Approximately 5 mln people a year, or about 14,000 daily, get infected with the virus which causes AIDS and 3 mln die annually from the illness.

Berkley said governments must boost contributions for developing a vaccine, as drug companies and charitable groups cannot be expected to do all the research

'There's not the market drive' amongst companies to 'invest the large amount of capital needed', he said.

Around 650 mln usd is spent annually by governments and corporations on AIDS vaccine research.

Berkley is calling for that amount to be doubled to 1.1 bln usd.

He said this sum is still small when set against the 70 bln usd spent globally each year on total health product research and development.

Berkley also answers those who say funds spent on researching a vaccine would be better spent on prevention

He says that even a partially effective vaccine could have a big effect in curbing HIV's spread.

He cites a study funded by the World Bank and European Commission, which suggests that a vaccine

 with 50 pct efficacy could cut new infections by up to 60 pct.

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