GENE SENTRY
Researchers say HLA-B variants can detect HIV as an "intruder" and signal the immune to fight it off
Promising inhibitor drug v. resistant HIV
BOSTON, Massachusetts
An international team of researchers found promising results of an experimental drug for HIV sufferers with resistance to most treatments. The inhibitor TMC114/r is described as very promising in trials on a group of 497 people who had already received a cocktail of drugs to no avail, reported Dr. Richard Haubrich at the 12th annual conference on retroviruses in February.
Haubrich, a scientist at University of California in San Diego, said the viral potency was down 97 percent on the study group and the drug's effect lasted throughout the 20 weeks of the trial. Treated with 600 milligrams of TMC 114/5 twice daily, the group also showed limited side effects from the drug, he said.
TMC 114/r is a novel protease inhibitor that previously has shown potent activity in resistant patients in a 14-day trial. Inhibitors block the important HIV enzyme protease, suppressing its effective reappearance and infection of other cells.
Dr. John Mellors of Pittsburg School of Medicine in Pennsylvania said: "TMC 114/r is the more promising inhibitor in the pipeline." It is produced by Belgian company Tibotec and Brazil's UNICAMP.
Scientists discover how AIDS virus attacks the body
BOSTON, Massachusetts
The discovery of a key element in the workings of HIV could eventually lead to the creation of effective vaccines against the virus. Published in Nature, the discovery shows how HIV mutates and provokes changes that permit it to enter cells.
The study was done at the Boston Children's Hospital and Harvard Medical School by Stephen Harrison, head of a research team at the Howard Hughes Medical Institute. The scientists were able to obtain a three-dimensional image of the protein gp120, an element of the HIV membrane, before it metamorphoses and attaches itself to a cell's CD4 receptors. Once the protein attaches to the receptors, HIV is able to penetrate the cell's interior and reproduce.
Understanding gp120's shape changes before the attack on cells could lead to the creation of new HIV vaccines. "Knowing how gp120 changes shape is a new route to inhibiting HIV by using compounds that inhibit the shape change," said Harrison. "The findings also will help us understand why it's so hard to make an HIV vaccine, and will help us start strategizing about new approaches to vaccine development."
Prototype French treatment cuts viral load
PARIS
French doctors have issued a highly encouraging report about a test treatment that slashed levels of the AIDS virus among a small group of HIV-infected volunteers. The prototype is called a therapeutic vaccine but this is something of a misnomer, for it is not a preventive vaccine in the conventional sense. Instead, it is more of a treatment, seeking to reduce levels of HIV among individuals already infected.
Researchers recruited 18 Brazilian patients chronically infected with HIV who were not receiving antiretroviral treatment. The volunteers received a mixture of their own dendritic cells and inactivated HIV to prime their immune system.
Dendritic cells are early defensive cells that rush out to meet an intruder and destroy it with enzymes. They then carry a chemical "tag," an antigen, on the surface of their cell that corresponds to the signature of the intruder. It is this tag that helps alert lymphocytes, the heavy artillery of the immune system.
A slippery foe, HIV is able to sidestep the dendritic cells, although how this is done is unclear. The goal of the experimental treatment, using the inactivated HIV, was thus to stimulate the dendritic cells so that they recognized the virus. The treatment was delivered in three injections, each a fortnight apart. There were no side effects.
Four months after the first dose, the viral load--the quantity of HIV in the blood--had fallen on average by 80 percent. A year after the jabs, eight out of the 18 patients still showed viral loads that had diminished by more than 90 percent.
Four of them had a viral load of less than 1,000 particles per milliliter, "which, in theory, means they are not infective," said chief researcher Jean-Marie Andrieu.
These results suggest that dendritic-cell therapy could be a "promising strategy" for treating people with HIV, says Andrieu's team.
Vaginal gel could block AIDS spread
SYDNEY
An Australian drug company has developed a vaginal gel that could halt the spread of AIDS. Starpharma said the water-based VivaGel proved successful in animals, and a first phase of human clinical trials has been completed.
"It works by preventing the AIDS virus from attaching to and infecting human cells," Starpharma scientist Alex Szabo said. "Women would apply the gel as they might a vaginal lubricant or something like that and then that provides a chemical protection [against] the infection process," he said.
The gel sticks to HIV at a molecular level, blocking its ability to attach to healthy cells.
A first testing phase found the gel produced no ill effects in women. Starpharma now plans to proceed to the next clinical trials. Even if the trials are successful, it will be several years before the gel is made commercially available, he said.
Gene clue throws light on HIV vulnerability
PARIS
Researchers say they had pinpointed gene variations that could explain why some people are more vulnerable to HIV than others, a finding that could also boost the quest for an AIDS vaccine. The variations are located in genes that control signaling molecules called human leukocyte antigens (HLA), which help identify an intruder and tell the immune system to destroy it.
The scientists took blood from 375 women with HIV in southern Africa who were not receiving anti-AIDS drugs, and analyzed the samples to get their HLA profile. There are three types of HLA--A, B, and C. Women who had one of two "protective" versions of HLA-B were likelier to survive and less likely to transmit the virus to their babies during pregnancy than counterparts who had one of two "deleterious" versions.
The study published in Nature adds to previous work that also points the finger at HLA-B variants. That research, conducted among Caucasians, found that individuals with certain types of HLA-B genes had less virus in their bodies and a higher tally of CD4 immune cells, which are targeted by HIV.
"Differences in viral load and absolute CD4 count, and by inference, in HIV disease outcome, are principally related to HLA-B allele [gene variant] expression," the Nature study says.
The work is a joint project by the universities of Oxford, Harvard, and KwaZulu-Natal, led by Oxford specialist Philip Goulder.
The search for an AIDS vaccine has been deeply frustrating. One reason is that no one has ever been found to have the "natural correlates" for immunity against HIV. If that individual exists and can be located, that would help vaccine engineers to mimic the workings of his or her immune system to design a protective formula.
Even though no one has yet been found who is immune to HIV, there is sufficient variety in the human immune system to expose potential chinks in the virus's armor. Some individuals can survive for years without having any of the symptoms of AIDS, whereas others very quickly develop the disease. Understanding and exploiting the genetic reasons for this big difference can help the search for a vaccine that may at least give partial protection.
Viagra blamed for AIDS resurgence in US
WASHINGTON
The United States is losing ground again in its fight against AIDS with blacks, particularly African-American women, suffering most from the resurgent spread of the virus.
Health experts blame a lack of education resources while American adults are showing growing complacency to the risks they run.
The number of cases fell by 50 percent from 1993 to 2001, before rising two percent in 2002, according to the Centers for Disease Control and Prevention (CDC). The number of deaths hit an annual peak of 52,000 in 1995 before seeing major falls with the advent of new drugs. The deaths continued to drop through 2001, but in 2002 rose to 16,371. More than 500,000 people are now believed to have died from AIDS in the United States, with almost 900,000 estimated to be infected with the virus.
"It's a pretty bad situation," said Sherry Kaplan, coordinator for the Center for Positive Connection in Miami. Kaplan said that people now show "a more casual attitude" to sex because they believe medication will help them with AIDS.
The growing use of treatments for male sexual dysfunction has contributed to the new spread of AIDS. There has been a 17-percent increase in cases in Florida among people aged over 55. "It's a new phenomenon," Kaplan declared. "Viagra is steering more infection because these men can now have sex and these [divorced and widowed] women don't know how to negotiate condom use, or they would never think that a man over 55 would give it to them."
"There are also people out there, probably a small proportion, who want to get it because of the benefits," she added. People with HIV get increased welfare and housing payments in Florida.
While AIDS now hits all sections of the US, minority groups are at particular risk. More than 50 percent of new cases recorded in the US in recent years are black, 72 percent of them women.
Cheap antibiotic slashes deaths among children
PARIS
A common antibiotic that costs less than 10 US cents per person a day can dramatically cut the death rate among children with the AIDS virus, according to a study in Zambia published in The Lancet.
Co-trimoxazole, one of the cheapest antibiotics in the world, was used in a test that involved 534 Zambian children under 15 who had HIV. Half of the children were given the drug each day in the form of an oral dose; the other half were given a placebo. When researchers did a follow-up 19 months later, they found that 74 (28 percent) of the children in the co-trimoxazole group had died, while 112 (42 percent) had died in the placebo group.
The findings were so remarkable that the study was discontinued on ethical grounds. The placebo group was immediately put on co-trimoxazole. The clinical reason for the success is unclear, but it is thought the drug combats pneumonia and tuberculosis bacteria that commonly claim the lives of people whose immune systems have been wrecked by HIV.
Doctors traditionally are opposed to long-term uses of antibiotics on the ground that this can build resistance to the drug. But the authors, led by Diana Gibb of Britain's Medical Research Council (MRC) said they found no evidence that the drug became less effective by the time the follow-up check was carried out. In addition, the drug was well tolerated by the children, and few were allergic to it.
They contend that the results are so emphatic that co-trimoxazole should be administered as a matter of course to all children in Africa who have been diagnosed with HIV.
Of the 534 children who took part in the study, only five percent received antiretrovirals.
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