INEFFECTIVE DIAPHRAGM
African trial yields disapointing results; researchers identify chink in HIV armor, raising hopes for vaccine
Natural molecule could help fight HIV
WASHINGTON
A naturally produced molecule that helps the body's immune system fight HIV could be used to stop cell destruction by the virus, according to a study published recently.
HIV attacks the body's defense system by hiding inside T-cells, researchers from the National Institute of Allergy and Infectious Diseases said.
As the illness progress, the T-cells, and even those not infected with HIV, are weakened and begin to self-destruct in a process known as apoptosis.
But researchers found that adding the molecule called interleukin 7 (IL-7) to blood samples from 24 HIV-infected patients at varying stages of infection reduced the levels of cell destruction.
The effects differed according to the level of infection, but initial results showed that the molecule could be used with antiretroviral drugs to help rebuild damaged cells, the researchers said.
Diaphragm disappoints in key African trial
PARIS
An HIV-prevention trial using the diaphragm has dealt a fresh blow to hopes for a shield, other than a condom, that African women can use to protect themselves against the AIDS virus.
The trial involved 4,948 women in Durban and Johannesburg, South Africa, and Harare, Zimbabwe, who were sexually active and did not have HIV. All were given an HIV-prevention package, comprising condoms, tests for HIV before and after the trial, and intensive counseling in safe sex. Half of them were then given diaphragms and lubricant gel, in addition to the condoms. The other half served as the control group and only had condoms.
The researchers found that there was no difference in HIV-infection rates between the two groups. Based on a benchmark of prevalence (100 woman years), the incidence was 4.1 percent for diaphragm group and 3.9 percent for the control group. The apparent reason: the diaphragm users, despite the safe-sex counseling, used the condom far less than their "control" counterparts.
The study, appearing in The Lancet, was headed by Nancy Padian of the University of California at San Francisco.
Despite their disappointment, the authors are intrigued that the diaphragm users did not have an increased rate in infection when they abandoned the condom, and call for further research into this phenomenon. Even so, "our findings do not support addition of the diaphragm to current HIV strategies," they say firmly.
The study was based on evidence that the cervix- the top of the vagina, which is covered by a diaphragm-has a concentration of cell types which the AIDS virus favors as a docking point. It latches onto such cells to infect the immune system.
Other research has shown that a diaphragm offers protection against chlamydia and the human papillomavirus, which raises the risk of HIV infection.
Another avenue being explored is a microbicide gel that a woman could place in her vagina to block or kill HIV. But so far, the results there have also been disappointing and even harmful.
"Women who cannot convince their male partners to use condoms are still in urgent need of a female-controlled method of protection," the study observed.
Atomic-scale pictures show chink in HIV armor
PARIS
Researchers have a rare piece of good news in the struggle against AIDS, saying they have identified an area of the virus that revives hopes for an antibody-based vaccine. Mutating and slippery and with several lines of defense, HIV has been the most redoubtable foe that vaccine designers have ever faced.
Attempts to engineer a classic preventive vaccine that stimulates antibodies-the first line of the body's defenses-have been thwarted by the virus's swift and constant genetic switches. This daunting, shape-shifting ability means that an antigen, a piece of the virus that is used to prime antibodies, is out of date by the time these defenders encounter a real-life viral intruder. HIV also has a cloak of sugary molecules that prevents antibodies from slipping in and blocking the virus from docking onto an immune cell, the first step toward infecting it.
These were among the problems to explain the frustrating failure of AIDSVAX, the only prototype vaccine that has gone through the long and costly three-phase process of tests for safety and effectiveness.
After this setback, researchers in AIDS vaccines almost gave up on antibodies. The big focus today is on priming T-cells to recognize and destroy the virus, which arguably makes it less a vaccine and more a treatment.
But a team of US scientists, reporting in Nature, says they have taken an atomic-scale snapshot of a key location on the tip of the virus's docking spike, called glycoprotein 120 (gp120), that is stable and not mutating-in other words, a fixed target. Even better, this location on gp120 is recognized by a specific antibody called b12, found in the blood of people who are able to hold the virus at bay for long periods. By latching onto a virus, an antibody can neutralize it. In plain language, it's like putting a piece of chewing gum on the tip of a key to prevent it from fitting into a lock. Antibodies also alert the rest of the immune system to come and destroy the germ.
Elias Zerhouni of the US National Institute of Allergy and Infectious Diseases, where the work was carried out, said the study showed a gap in HIV's armor. "One of our primary goals is to develop HIV vaccines that can stimulate broadly neutralizing antibodies," said Gary Nabel, coauthor of the paper. "The structure of this gp120 epitope (recognition site), and its susceptibility to attack by a broadly neutralizing antibody, shows us a critical area of vulnerability on the virus that we may be able to target with vaccines. "This is certainly one of the best leads to come along in recent years."
Wayne Koff, a top scientist at the International AIDS Vaccine Initiative, which cosponsored the research, said promising new paths had been opened up in an arduous quest. "This work uncovers a potential HIV vulnerability that provides an important direction for the design of novel vaccine concepts," Koff saidl. "[It] is further evidence that an effective, preventive AIDS vaccine is possible."
New drug set for testing in China
BEIJING
A new anti-HIV drug developed by Chinese scientists has been licensed for clinical testing. Nifeviroc, which works by inhibiting CCR5, a protein that commonly exists on the surface of human immune cells, is set to become China's first entry-inhibitor for HIV treatment, the China Daily said.
"The CCR5 protein provides a medium through which the HIV virus can infect healthy cells," said Ma Dawei, a researcher with the Shanghai Institute of Organic Chemistry involved in the drug's development. "By deactivating the protein, the virus can be stopped before it enters the cell."
The report said early tests have indicated that nifeviroc, which is taken orally, has promising antivirus capabilities and few side effects. Hopes are high that it can provide an effective barrier against HIV. But scientists said it will be a further three to five years before the drug is ready to be put into clinical use.
An American company is currently involved in the third-phase clinical testing of a drug with a similar mechanism to nifeviroc and which is expected to become the world's first oral HIV entry inhibitor.
Integrase inhibitor shows unprecedented results
PARIS
A new category of drug has shown promising results for HIV/AIDS patients who failed to respond to other treatments, a recent study showed.
Especially when combined with other medications, raltegravir-the first in a new class of antiretroviral drugs called integrase inhibitors-dramatically reduced the presence of HIV and boosted immunity in clinical-trial patients, according to the study in the The Lancet.
Integrase inhibitors act by targeting and disrupting an enzyme that facilitates the insertion of the HIV into the host's cellular genome.
In clinical tests on 178 patients with advanced HIV infections that had proved resistant to standard treatments, raltegravir "showed unprecedented levels of virological efficiency," virologists Pedro Cahn and Omar Sued wrote in an accompanying commentary. The treatment "achieved virological suppression even in patients with limited options," they said, predicting that the new drug would "have a major role in salvage therapy," the term used to describe last-ditch efforts to save those with highly compromised immune systems. "Clearly, we are in a new era of antiretroviral therapy."
There are three types of enzyme needed for HIV to replicate, namely reverse transcriptase, protease, and integrase. Up to now, no drug has successfully inhibited integrase enzymes.
A team of researchers at Merck Research Laboratories in Westpoint, Pennsylvania, led by Beatriz Grinsztejn, divided the 178 patients into four groups during clinical trials.
Each of three groups were given different doses of raltegravir, ranging from 200 to 600 milligrams, and the fourth group received a placebo. All four also took a basic "background treatment."
After 24 weeks, the amount of HIV genetic material in the blood dropped below a measurable threshold (50 copies per milliliter) in 65 percent of the patients taking raltegravir, nearly five times as many as the placebo group. Immune-system responses were also dramatically improved.
"If no long-term unexpected side effects or resistance issues emerge, raltegravir will have a major role in salvage therapy, particularly in combination with another new drug," Cahn and Sued concluded.
Experimental vaccines offer limited immunity
CHICAGO
Scientists say the most promising of the many experimental HIV vaccines in development offer only limited immunity against the deadly virus. Unlike classical vaccines, the first-generation HIV vaccines will not enable people to fight off the virus, but may protect their immune system from the worst ravages of the virus and delay the onset of AIDS.
And because patients are at their most infectious when viral levels are high, such vaccines might also reduce the spread of the sexually transmitted infection, making it a useful tool for public-health authorities battling to contain the global HIV/AIDS pandemic.
"There is optimism that even a less-than-perfect vaccine could benefit both individual recipients and the at-risk community," said the authors in a commentary published in the New England Journal of Medicine.
It is still not clear when the first vaccines will be available. However, phase-I and -II clinical trials are "well into their execution. Large numbers of people are being vaccinated," said Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases and one of the authors of the paper.
Researchers around the globe have been searching for a vaccine against HIV for two decades, but efforts have been thwarted by the virus's ability to mutate and evade clearance by the immune system. Eventually scientists turned their attention to so-called T-cell vaccines that primarily induce a cellular immune response that reduces viral levels and preserves critical cells needed to control infection.
In animal studies, peak viral levels were reduced by a factor of 10 in primates that were inoculated with these types of vaccines and then infected with the simian counterpart of HIV, according to the paper. The inoculations also "dramatically" slowed the progression of the disease in many animals, Fauci said.
The hope is that an effective human T-cell vaccine could substantially improve the quality of life for people who contract the virus after immunization by postponing the day when they develop AIDS and have to begin treatment with a daily cocktail of drugs. Also, by stifling the initial burst of virus and better controlling virus levels, an immunization program could potentially curb the spread of the epidemic, which is largely driven by people who have viral loads.
Computer-modeling studies have suggested that even a vaccine that does not provide adequate protection against infection might alter the course of the epidemic, but further studies will be needed to test the hypothesis, the authors said.
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