Searching for an anti-HIV cream

“There’s a dance between the virus and the immune system,” says Dr Angela Obasi from the Liverpool School of Tropical Medicine. “The more we understand about the virus, the more we understand that dance”This poetic description captures a grim reality - the behaviour of the HIV virus, like a complicated dance, is extremely difficult to predict and therefore tough to combat.“Every time you come up with a strategy to combat the virus, the virus comes up the a strategy to overcome your strategy,” explains the senior clinical researcher, who has been working in HIV research since 1996. The latest addition to the armoury of anti-HIV strategies is a gel that blocks the “keyhole” in the body’s first line of defence - preventing the virus from entering cells.his gel, developed by an international team of researchers and published in the journal PLoS Pathogens, plays a clever trick on HIV - blocking the receptor that HIV latches onto in order to gain access to an immune cell.“The idea here is that you’re blocking up that CD4 keyhole so the virus can’t enter the [immune] cell,” explained Dr Obasi. Lead researcher in the development of this gel, Loic Martin from CEA, a molecular research institute in Gif-sur-Yvette, France, described the results as “promising”.One advantage of this potential, he explained, is that this is an entirely new kind of compound which is not currently used in HIV research. “It may prevent the spread of viruses that become resistant to current treatments,” Dr Martin told the BBC.At this stage, though, the product has only been tested in non-human primates. It will be up to five years before it is tested on human patients. And efforts to develop similar anti-HIV gels, or microbicides, have presented a great deal of frustration in the fight against this global epidemic.The discovery that sparked the initial hope for microbicide gels came in the 1990s, when a long-used spermicide gel called nonoxynol-9, which is still used in many brands of condom, was found to destroy the HIV virus in a test tube.But subsequent clinical studies revealed that, rather than protect against infection, the gel made it worse. “It caused inflammation,” explained Dr Obasi. Immune cells that flood to the site of this inflammation are the very cells that the HIV virus “really likes to lock on to”. “They’re the ferries that take the virus into the body,” she said.Even as recently as 2007, a product called Ushercell, which has made it to late-stage clinical trials, was withdrawn for the same reason - it made HIV infection worse.Michael Lederman, director of the Center for Aids Research at Case Western Reserve University in the US, admitted that tests of some of the first prospective anti-HIV gels had been problematic.“Some early efforts at topical prevention [used] agents that had broad activities that did not target the virus specifically. Some had detergent activities that were toxic to the lining of the vagina,” he explained. “Newer agents that target the virus more selectively are much more likely to prove effective and useful.”According to the Microbicide Trials Network, there are currently nine different microbicide products in clinical trials. Dr Obasi says that some are now showing genuine promise.“There’s been a great amount of energy put into [developing these] creams or gels that a woman could put into the vagina before sex,” she explained, “because so many women are powerless to protect themselves against HIV”.In sub-Saharan Africa, where the epidemic is at its worst, more than 60% of all new HIV infections are women. Dr Obasi continued: “In many parts of the world - especially in the parts of the world where HIV is most prevalent, there are gender status issues that make it very tricky for a woman to control the circumstances under which she is exposed to HIV.”“So methods that are controlled by women give them a critically important power over the safety of their own bodies.”Women in many sub-Saharan African countries face being stigmatized if they insist on using a condom - this is associated with promiscuity and sex work. There have even been reports of police in countries including Kenya, Namibi, South Africa, Zimbabwe of police confiscating condoms from sex workers to use as evidence of prostitution. In 2011, the New York Times reported that police in the US were threatening to arrest sex workers if they found them carrying “more than a couple” of condoms.Searching for a cureThe search for the ultimate weapon - an effective HIV vaccine - continues. One exciting potential treatment was an experimental vaccine tested on 16,000 people in Thailand, and was found to reduce rates of infection by almost one third.Peter Godfrey-Faussett, senior science adviser to the UNAIDS programme, said that this was an “exciting development”. “My own feeling is that HIV vaccine research we’re still waiting for the big breakthroughs,” he told the BBC.“People will need to combine a variety of approaches to achieve as low a risk as [possible].”“And that doesn’t mean we move away from the basics - condom use and responsible sexual behaviour.”Prof Godfrey-Fausset added that clinical trials of potential treatments were becoming increasingly expensive. “Scientifically it becomes harder to show that the new thing works,” he explained. “We need bigger and bigger clinical studies and that means fewer studies can be afforded. “This makes it even more important that scientists that produce things at the basic level get as far as possible with development, so we’re only testing the products that are most likely to succeed.”Both Dr Obasi and Prof Godfrey-Fausset said they were hopeful that they would see a cure developed during their own research careers. But a self-administered gel is one of the most highly prized goals in the battle against the epidemic.“Female-controlled methods of HIV prevention are extremely important,” said Prof Godfrey-Fausset, “so we need a big pipeline of products to ensure that some of them succeed. “It’s important that research like this is funded, because it’s a realistic way to make a difference to millions of women’s lives - not just in sub-Saharan Africa, but throughout the world.”BBC

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Searching for an anti-HIV cream