News (Updated August 1, 2010)

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Anti-HIV Gel Cuts Infection Risk in Half

The new gel would be a huge benefit to African women bearing the brunt of the AIDS pandemic.

Jul 19, 2010 AFP

Scientists on Monday reported a major stride towards a vaginal gel that can thwart HIV, a goal that would be a huge benefit to African women bearing the brunt of the AIDS pandemic.

A prototype cream tested in South Africa reduced the risk of infection by the human immunodeficiency virus (HIV) by 39 percent overall, but by 54 percent among those women who used it most consistently, they said.

The study coincided with the six-day 18th International AIDS Conference, which opened in Vienna on Sunday.

The results must now be validated in a third, wider phase in the arduous process of assessing a new medication for safety and effectiveness.

Although several questions have yet to be answered, the findings are a bright ray of hope in the 29-year campaign against acquired immunodeficiency syndrome (AIDS), the researchers said.

"Without this gel, we may see 10 women becoming infected in a year. With this gel, we would see only six women becoming infected," said Salim Abdool Karim, one of the two leading co-researchers, in a teleconference with reporters.

Twenty-five million people have died from AIDS and more than 33 million others today are infected by HIV, which causes the disease.

More than two-thirds of these live in sub-Saharan Africa , where 60 percent of new infections occur among women and girls.

One of the big vectors of transmission is through coercive intercourse by an infected partner who is unwilling to wear a condom.

The gel that was tested contains a one-percent formulation of tenofovir. It is a frontline component in the "cocktail" of antiretroviral drugs that disrupt HIV reproduction in immune cells.

Previous microbicides that have been tested have not contained an antiretroviral, and have had either a very low level of protection or even boosted the risk of infection.

Over nearly three years, the gel was tested among 445 HIV-negative women, while 444 counterparts received a harmless lookalike called a placebo.

They were then tested for HIV at monthly follow-up visits, where they were also given counselling in safe sex, access to condoms and treatment for sexually-transmitted disease.

Each participant was asked to insert, using a vaginal applicator, a first dose of the gel within 12 hours before sex followed by a second dose as soon as possible but within 12 hours afterwards, said co-leader Quarraisha Abdool Karim, also of the Centre for the AIDS Programme of Research in South Africa (CAPRISA) in Durban .

Compared to the placebo group, the gel reduced the risk of HIV infection by 39 percent overall, but by 54 percent among women who adhered to the instructions most faithfully.

There was no increase in side effects, nor -- among women who became infected with HIV -- any sign that they were more resistant to tenofovir as a result of the gel.

Despite this good news, the scientists said they still had to tackle several important issues.

One is why the gel seemed to be less effective after about 18 months.

This may be due to weakened adherence to the cream, they suggested. About 40 percent of the women in the trial used the microbicide less than one time out of two.

The trial was conducted in an urban setting (Durban) and a rural setting (Pietermaritzburg) KwaZulu-Natal province, enrolling sexually active women aged 18 to 40 considered to be of high risk of exposure to HIV.

It was a so-called IIb trial, meaning that it had passed earlier scrutiny for safety and effectiveness, but was still relatively small compared to a Phase III test involving several thousand volunteers.

The study, published by the journal, Science, was to be the focus of a seminar on Wednesday at the world AIDS forum.

If -- eventually -- the gel is approved for use, it will join a small but growing arsenal of preventative tools against HIV.

For a long time, the condom was the only method that had a confirmed high degree of protection from HIV in intercourse.

Four years ago, it was joined by male circumcision. Removal of the foreskin, which contains cells that are vulnerable to penetration by HIV, can reduce HIV risk by more than half, but only for men and not for women.

Availability of a microbicide that is 60 percent effective would avert two and a half million infections over three years, according to a 2003 mathematical study.

Island Monkeys Give Clues to Origins of HIV's Ancestor

by Jon Cohen on July 29, 2010

VIENNA —Thousands of years ago, a piece of West Africa separated from the mainland and formed the island of Bioko . The monkeys that inhabit the island may be crucial to unraveling the puzzling origins of the AIDS epidemic in humans, according to a study presented here last week at the 18th International AIDS Conference.

Scientists have argued about the origin of the AIDS epidemic since it surfaced in 1981, but this much is widely accepted today: Sometime around 1931, HIV-1, the main virus driving the epidemic, likely entered humans from chimpanzees, which are infected with a related virus called SIVcpz. The chimp virus, in turn, is a blend of SIVs from two different monkey species.

Less clear is when the monkey viruses moved into chimpanzees. Last year, one prominent investigator in the origin field, evolutionary biologist Michael Worobey of the University of Arizona in Tucson , found evidence that the monkey-to-chimp jump occurred sometime between 1266 and 1685. Worobey and his team used changes in the RNA of these SIVs to calculate their age. These so-called molecular clocks depend on how they're calibrated, however, and not everyone was convinced.

Skeptics, including virologist Preston Marx of the Tulane National Primate Research Center in Covington , Louisiana , suspected the leap from monkeys to chimps occurred tens of thousands of years earlier. SIVs and SIVcpz are found everywhere from East to West Africa , and Marx reasoned that it "was just not possible" for the viruses to have spread so widely in 500 years. So he came up with a new way to calibrate the molecular clock that relied on Bioko 's known separation date from the mainland, and he recruited Worobey to help him analyze the data.

Marx and his team collected samples of SIV in dead monkeys on Bioko , which were killed for bushmeat. The researchers isolated SIVs from four different species on the island. One species, the Bioko drill (Mandrillus leucophaeus poensis), has a mainland counterpart that also harbors SIV. The fact that the virus was in both drills and that the island separated from the mainland 12,000 years ago provided a precise way to calibrate the molecular clock, and comparisons of the SIVs confirmed Marx's suspicion that the jump into chimpanzees must have occurred much earlier than Worobey's previous estimates.

As it turned out, the SIV from the drills closely matches SIV from red-capped mangabeys, one of the two contributors to SIVcpz. So an ancestor of this drill could have infected chimpanzees. According to Marx's analysis, a virus related to the Bioko drill's SIV infected chimpanzees at least 22,000 years ago.

Worobey's earlier studies did not date the origin of SIV itself but suggested that it was "relatively young." Others have argued that the SIVs emerged millions of years ago. The new analysis of all four monkey species suggests that, at a minimum, the SIVs are 76,000 years old—although Marx suspects that they evolved far earlier. This longer history of primates harboring the viruses may explain why SIVs cause no harm in the African monkeys they infect, Marx noted: The hosts have had more time to evolve appropriate immune responses or cellular changes that make them less vulnerable to the viruses. (Recent reports strongly indicate that SIVcpz can cause AIDS in chimpanzees.)

"The data are excellent," says Simon Wain-Hobson, a virologist at the Pasteur Institute in Paris who has been involved in origin studies since the start of the AIDS epidemic. But he cautions that the SIV on the island may have been introduced recently, upending Marx and Worobey's clock calibration. "The jury is out," says Wain-Hobson, noting that he is not ready to discard the substantial evidence from other molecular-clock analyses that SIVcpz is younger.

Paul Sharp, an evolutionary biologist at the University of Edinburgh in the United Kingdom who first described the SIVs that led to SIVcpz, has more confidence that the new findings will hold up to scrutiny. "Molecular-clock analyses have suggested that the SIVs arose within the last few thousand years," he says. "These Bioko viruses are clear evidence that the SIVs must be much older than that."

Anti-HIV Gel Also Effective Against Herpesvirus

by Jon Cohen on July 20, 2010

VIENNA —A widely anticipated presentation here at the 18th International AIDS Conference turned out to be doubly sweet. As Science reported yesterday, researchers have announced that South African women who received a vaginal gel that contains the anti-HIV drug tenofovir had a 39% lower chance of becoming infected by the virus than did those who received a placebo. But the researchers are also reporting that the microbicide gel had an even more powerful effect against herpes simplex virus-2 (HSV-2).

"It's very interesting and clearly needs to be followed," says Zeda Rosenberg, who heads the International Partnership for Microbicides, a nonprofit based in Silver Spring , Maryland .

Quarraisha and Salim Abdool Karim, the husband-and-wife team who led the study, called CAPRISA 004, presented the bulk of the data during an afternoon session today. As Salim explained, nearly half of the women did not have HSV-2 infection at the start of the study. Of this group, 58 of 224 women in the placebo arm of the study became infected with HSV-2 versus 29 of the 202 who received the gel. The difference, 51%, was statistically significant, and the microbicide's effect on HIV infection was independent of the HSV-2 finding, noted Salim Abdool Karim.

The finding is especially heartening because HSV-2 infection increases a person's risk of becoming infected by HIV-1. "Once confirmed and replicated, tenofovir gel has the potential to alter the course of the HIV epidemic," said Salim Abdool Karim.

As he explained, a precursor compound to tenofovir actually is a marketed drug to treat HSV-2 infection. But few AIDS researchers knew the connection, and many were stunned that tenofovir had such a powerful impact on HSV-2.

"It goes to show that sometimes you learn unexpected things from well-designed science projects," says Robert Grant of the University of California , San Francisco , who is studying a related prevention strategy that uses an anti-HIV pill to protect uninfected people. "It's a nice example of how prevention interventions can synergize with each other."

Therapeutic HIV vaccines show promise

Clinical trials hint that treatment strategy is not a dead end.

Alison Abbott

The world buzzed last week with news that an antiretroviral gel can halve the incidence of HIV infection in women (see Nature doi:10.1038/news.2010.363; 2010).

But a quieter buzz could be heard at the International AIDS Conference (AIDS 2010) in Vienna , where the gel results were unveiled. At a special session, included in the programme at the last minute, attendees heard the results of a handful of successful, but small, early-phase clinical trials for therapeutic vaccines — once thought to be a dead end for tackling HIV.

Normal vaccines are designed to prevent infections, but so far none has worked for HIV. Therapeutic vaccines, in contrast, aim to treat infected people — in the case of HIV, by boosting ravaged immune systems. Initial clinical trials in the 1990s were disappointing, however, and the vaccines fell from scientific fashion.

Drug combinations that decrease viral concentrations have become the main method of treating HIV, but they do not completely suppress the underlying disease. "They leave patients with a level of harmful immune activation, which can cause premature ageing," says Joep Lange, a clinical virologist from the University of Amsterdam and a former president of the International AIDS Society. "The therapeutic vaccine approach may help with this", he says, by modifying immune responses.

Lange is encouraged by the trial results, but cautions that the trials so far are small, and that even if the vaccines work they will never replace drugs. Some key AIDS researchers continue to believe that therapeutic vaccines will not prove helpful in the long run.

All of the vaccines, which were developed by several small biotechnology companies, modestly but significantly reduced viral levels in the blood of patients, who responded for months or longer. In some cases, the vaccines also increased levels of CD4+ T cells — the vital immune-regulator cells that HIV depletes. In theory, the vaccines would only need to be administered every few months.

Two of the phase II trials reported at the meeting focused on improving the efficiency of the immune system's dendritic cells. These are the cells that present foreign antigens — in this case, HIV proteins — to T cells so that they can recognize and eliminate the invaders.

“You can’t shut doors when options are so limited.”

One approach, developed by Genetic Immunity, a biotechnology company based in Budapest , involves creating nanoparticles that contain selected pieces of RNA from HIV. The preparation is applied to patients by means of a skin patch. The skin below the patch is first slightly damaged to attract precursors of dendritic cells, exposing them to 15 HIV proteins transcribed from the RNA.

The other tactic, from Argos Therapeutics of Durham, North Carolina, relies on tailor-made vaccines for each patient. The researchers extracted dendritic cells and viral RNA from patients, then loaded the cells with the RNA before putting them back into the same patient.

Therapeutic vaccines are normally tested in patients who are already undergoing drug treatment. To avoid the drugs confounding the results, patients are required to take a drug 'holiday' for the few months of the trial. But a placebo-controlled clinical trial by FIT Biotech of Tampere, Finland, broke with that model by recruiting 60 patients in South Africa who had never been treated with drugs.

The FIT vaccine comprises a combination of gene fragments designed to make the patient immune to six viral proteins. In around 80% of patients receiving treatment, the virus was suppressed and CD4+ levels were maintained two years after therapy began.

The results are particularly relevant to countries such as South Africa , where many patients do not have easy access to drugs, says Eftyhia Vardas, a virologist at the University of the Witwatersrand, who ran the clinical trial in 2006 in Soweto , Johannesburg . Vardas recalls feeling like a 'maverick' when she agreed to take on the trial. At the time, the South African government officially denied that HIV caused AIDS, and her scientific colleagues didn't believe that therapeutic vaccines held any promise. She was sceptical herself, she says, having seen other trials fail.

"But you can't shut doors when options are so limited," she says. South Africa is home to 5.7 million HIV-infected people. A vaccine, says Vardas, "would help South Africa to be able to delay onset of AIDS and reduce infectivity by keeping viral loads low when drugs are not so widely available".

The ultimate value of the vaccines will only become clear as larger phase III trials roll out over the next few years. For now, leaders in AIDS research are cautious about the results. Anthony Fauci, director of the US National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda , Maryland , says that he could imagine a role for "a good therapeutic vaccine" in patients who have been treated early in their disease, and therefore have only a small reservoir of HIV, and whose blood levels of HIV are completely suppressed by drugs. But he warns that because the vaccines caused only a modest decrease in viral load, using them in place of drugs could allow viruses to mutate beyond the control of the vaccine. "These early trials involve small numbers of people," adds Carl Dieffenbach, head of the NIAID AIDS division. "It would be wrong to foster false hopes."

But the Maryland-based advocacy group National Association of People with AIDS, whose vice-president of community affairs, Stephen Bailous, organized the special session, has championed the approach. "We need to have hopes and some of the therapeutic vaccines look really promising," says Bailous. "If we can't raise our hopes there, then where?" 

Malaria cases rise by 19% in Scotland

Malaria is spread by mosquito bites

Helen Puttick, Health Correspondent

29 Jul 2010

More travellers fell ill with malaria in Scotland last year, new figures revealed yesterday.

The number of cases increased by 19% to 44, reversing a previous drop in diagnoses.

The same trend was noticed across the UK . In 2009 there were 1495 cases, up 9% from 2008.

Dr Kitty Smith, medical lead for surveillance agency Health Protection Scotland, said the rise could be a “blip”.

There is hope that publicity surrounding Cheryl Cole, the pop star and X Factor judge who contracted malaria during a holiday in Tanzania, will raise awareness among young travellers about the importance of protecting themselves.

Smith said: “We do know that when a disease is highlighted in the media or when a celebrity – particularly one who appeals to the age group who are most vulnerable – catches a disease, it does have an effect. It has done in the past with diseases such as HIV.

“We have had comments to us from travellers saying they found out about malaria because they saw Cheryl Cole had the condition. So from a very anecdotal point of view and past experience, it is quite likely that it will have an impact.”

Malaria is spread by mosquito bites and symptoms include a fever, sweating and shivering, aching muscles and a headache. It is potentially fatal.

Researcher finds key to how AIDS infects cells

July 30, 2010

Debra Black

A scientist who heads the National Institute of Allergy and Infectious Diseases believes he may have found a key to how HIV manages to break through and infect a single cell.

It may all come down to a protein that acts as a receptor on CD4+ T-cells, said Dr. Anthony Fauci, director of the NIAID and a highly respected AIDS researcher, in an interview with the Star.

This protein – known as alpha 4 beta 7 – allows HIV to bind to the cells that are found beneath the vaginal and rectal mucosa. Then the virus begins replicating, explained Fauci.

Fauci, who discussed the discovery at a plenary session of the AIDS Conference in Vienna this month, believes that the interaction between the transmitting or infecting HIV and the receptor should be considered as a target for a vaccine against sexual transmission of HIV.

His was just one of several breakthroughs that have occurred in recent months, including work by fellow NIAID researcher Dr. Gary Nabel and Dennis Burton, director of the International AIDS Vaccine Initiative’s Neutralizing Antibody Consortium and a scientist at The Scripps Research Institute.

Nabel, the institute’s director of vaccine research, has found three antibodies that protect against a wide range of AIDS viruses. In a Reuters story, Nabel said that two of the antibodies attach to and neutralize 90 per cent of the various mutations of the human immunodeficiency virus that causes AIDS.

Meanwhile, Burton has found a component of an HIV surface protein that is stable and appears vulnerable to a specific antibody, known as b12, which neutralizes HIV.

The work of these three scientists may have long-term and profound implications for the development of a vaccine, something that has eluded researchers for many years.

“We’ve had so many disappointments with the HIV vaccine,” Fauci said. Most scientists, he added, are treading cautiously.

“I hope it will help open new vistas for vaccines,” he said of his discovery.

Researchers up until now have focused on developing a vaccine that would fight the various strains of HIV. Nothing has worked.

“HIV exists as a swarm of viruses that differ from each other even though they are all HIV,” Fauci said. “What is in your body changes and differentiates over time. It diverges from the original virus.”

Fauci suggests that his discovery might allow scientists to begin to build a vaccine against the transmitting virus and the site where the initial infection occurs.

Link between HIV drugs and heart attack

Study suggests greater heart attack risk associated with protease as opposed to integrase inhibitors

David Binning (Australian Life Scientist)

30 July, 2010

A study by Sydney researchers showing that the protease inhibitor type of HIV drugs carry a greater risk of heart attack than the new integrase inhibitor family of drugs is expected to lead to a greater understanding of the disease and how to treat it.

Associate Professor Katherine Samaras and Professor Andrew Carr at the Garvan Institute of Medical Research and St. Vincent ’s Hospital looked at the effects on blood fat metabolism of two HIV drugs; ritonavir, a protease inhibitor marketed by Abbott Laboratories as Norvir and Merck's new integrase inhibitor drug Raltegravir.

Ritonavir has been linked to numerous metabolic complications including higher fasting levels of cholesterol, while Raltegravir is known to have fewer metabolic effects.

The study involved 20 people, one half taking ritonavir and the other Raltegravir, who were measured after eating for different blood fat levels; a key indicator of heart attack risk. The researchers found that after one month, ritonavir caused “significantly higher” levels of the atherosclerosis-inducing LDL cholesterol after a meal, compared to raltegravir.

A unique aspect of the study was that it involved people without the HIV infection, allowing the researchers to more clearly ascertain the effects of the drugs without interference with other medications or the disease itself.

“While a few other studies have investigated post-meal blood fat and sugar metabolism, this is the most comprehensive study of the post-meal metabolic response with these medications to-date,´ said Associate Professor Samaras.

“About half the heart risk of protease inhibitor therapy has never been explained. Our findings of higher post-meal LDL cholesterol after food may explain at least some of this missing link in accelerated heart risk.”

The results represent an important step towards improving the health and quality of life of HIV sufferers.

“Our data may explain why patients receiving protease inhibitors have rates of heart attack that are higher than estimates derived from conventional heart disease risk calculators, which only use fasting cholesterol values,” said Professor Carr

“HIV patients may therefore need more aggressive management of heart disease risk than previously appreciated.”

Tuesday, July 27, 2010

Good early results for herpes vaccine

Boston Business Journal - by Julie M. Donnelly

Antigenics says it has achieved positive results in an early stage human trial for a potential herpes vaccine. A vaccine, if approved, would be a blockbuster pharmaceutical product — 60 million Americans are infected with herpes simplex virus-2, more commonly known as genital herpes.

Officials at the Lexington-based company say the findings show that Antigenics’ proprietary vaccine platform that is focused on so-called heat shock proteins, which are found in all cells and play a role in helping the immune system to recognize diseased cells. While the initial focus of development has been in HSV-2, Antigenics says the technology platform can potentially be utilized for treatment of many types of infectious diseases such as HIV, hepatitis, malaria and tuberculosis.

The potential vaccine would treat, not prevent, herpes. However the treatment, if effective, would decrease transmission of the disease.

The phase 1 study included 35 patients who had tested positive for herpes simplex virus - 2. The study showed that the majority of patients had two types of immune system responses to the vaccine.

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