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New hope for HIV microbicide

A new study has revived hopes for an effective vaginal microbicide in preventing the transmission of HIV. A compound widely used in cosmetics and foods can block transmission of the virus by interfering with the immunological steps to infection, linkurl:researchers report;http://www.nature.com/nature/journal/vaop/ncurrent/full/nature07831.html in Nature this week. Representation of virus expansionafter SIV exposure. Greencrosses: clusters of infected cells. Image: A. HaaseThe compound's microbi

By | March 4, 2009

A new study has revived hopes for an effective vaginal microbicide in preventing the transmission of HIV. A compound widely used in cosmetics and foods can block transmission of the virus by interfering with the immunological steps to infection, linkurl:researchers report;http://www.nature.com/nature/journal/vaop/ncurrent/full/nature07831.html in Nature this week.
Representation of virus expansion
after SIV exposure. Green
crosses: clusters of infected cells.

Image: A. Haase
The compound's microbicide potential has so far been tested in vivo only in monkeys, but in vitro results suggest it also works against the human version of the virus. "I think this is a really exciting study," said linkurl:Melissa Robbiani,;http://www.popcouncil.org/staff/bios/Robbiani_M/robbiani_m.bio.html senior scientist at the Population Council, a New York research and policy nonprofit focused on AIDS and reproductive health. To date, most microbicides under development work by simply blocking the virus from entering the body or target cells, said Robbiani, who was not involved in the research, "whereas this is actually targeting the immune system and modulating immune function." With a vaccine for HIV still years away, researchers have long pinned their hopes on a topical product that could be applied to the vagina to stem the virus's spread. The past few years, though, have brought dismaying results in microbicide development. In February, 2008, a promising microbicide gel called Carraguard linkurl:was deemed ineffective;http://www.the-scientist.com/blog/display/54312/ in a Phase 3 study. And the February before that, negative results from a Phase III trial linkurl:sank a potential microbicide;http://www.the-scientist.com/news/display/52861/ called Ushercell. linkurl:Ashley Haase;http://www.micab.umn.edu/faculty/Haase.html at the University of Minnesota, the current study's main author, and his colleagues began by mapping the innate immune response initiated locally in the vagina upon exposure to the virus. They observed growing clusters of infected immune cells in the vaginas of monkeys exposed to simian immunodeficiency virus (SIV), the monkey version of HIV. First, plasmacytoid dendritic cells rushed to the scene; those spurred a chemokine and cytokine response, which in turn brought CD4+ T cells. The T cells would then be infected by the virus, fueling its spread throughout the body, Haase and coauthor linkurl:Patrick Schlievert;http://www.micab.umn.edu/faculty/Schlievert.html explained in a press conference yesterday (March 3). The team reasoned that "if you could break one of the links in that chain, you would break the influx of target cells that the virus needed" to infect further cells, Haase said. They tested the compound glycerol monolaurate (GML) in that role because other research shows it appears to block the growth of microorganisms such as Staphylococcus and Chlamydia, and because it was already FDA-approved for oral and topical use. (GML, an ester, is commonly used as an emulsifier in cosmetics and foods such as ice cream.) In cultured human vaginal epithelial cells exposed to HIV, they found, GML blocked the production of molecules that appear during inflammation and that are thought to increase susceptibility to HIV infection. The researchers then made up a 5% GML solution dissolved in a lubricant called KY warming gel, and applied it to five rhesus macaques that had been vaginally exposed to SIV. The GML gel blocked acute infection in all five of the monkeys tested, while four out of five control moneys, exposed to the virus in the same way, became infected. "The results, we think, are very encouraging," said Haase in the press conference. The study not only demonstrated the efficacy of GML in blocking the virulence of immunodeficiency viruses, Robbinani noted, but it also "provided additional evidence for the innate response role in infection" and teased out the roles of different immune cells in propagating the virus. "That's important just from a biology standpoint," she said. Haase and Schlievert noted that further animal testing is needed before GML can be tested in humans. One of the five monkeys in which the gel was tested initially appeared to be protected from SIV, but months later developed the infection, they said; long-term studies will have to be done to understand how often such "occult infections" occur. "And we also need to find much better dosing schedules [that are] more applicable to the real world," Haase said in the press conference. Also, they cautioned, the compound's effectiveness in monkeys can't be extrapolated to humans. "Vaginal transmission by rhesus macaques is regarded by many as the best animal model for HIV transmission, but it's still an animal model," Haas said. Haase et al's study isn't the only positive recent news on the microbicide front. Last month, researchers from an international collaboration called the Microbicide Trials Network reported linkurl:promising results;http://www.ipm-microbicides.org/news_room/english/press_releases/2009/20090209_pro2000_buffergel_study.htm from a trial of another microbicide in development, PRO2002, a polymer intended to interfere in interactions between HIV and its target cells. Those findings, from a Phase II safety and efficacy study, prompted the Gates Foundation linkurl:to pump $100 million;http://www.google.com/hostednews/afp/article/ALeqM5iJKQ-a-4mDSbmAWE2et17l7o0obg into the International Partnership for Microbicides, a Maryland-based organization working on HIV microbicide development.
**__Related stories:__***linkurl:HIV microbicide by 2010?;http://www.the-scientist.com/article/display/22293/
[16th July 2004]*linkurl:Topical control of HIV transmission;http://www.the-scientist.com/article/display/13372/
[11th November 2002]
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Comments

Avatar of: anonymous poster

anonymous poster

Posts: 26

March 4, 2009

This is great news and very encouraging. But I must say I am curious why they used KY Warming Gel instead of regular KY as the carrier... I kind of doubt that the animals get the same erotic pleasure from it as the woman on the TV commercial does(?) One also might wonder if we can use hand lotion, or better yet, Ice Cream to make less-than-safe-sex safer.........\n\nBaxter Zappa
Avatar of: Philippe Laveaux

Philippe Laveaux

Posts: 5

March 4, 2009

So this GML microbiocide hinder molecules that helps makes us susceptible to contracting this disease. What molecules is this biocide hindering? Is it destroying the surface proteins that the virus needs to invade the T helper cells? Or is it killing off viral proteins the virus injects into the T cells to replicate itself?
Avatar of: anonymous poster

anonymous poster

Posts: 26

March 4, 2009

First and foremost, there is no animal model for HIV/AIDS. The chimpanzees originally utilized for study, back in the 1980's, never developed AIDS-related symptoms and/or disease processes, and were (ultimately) "retired" from the research investigation in recent times, alive and well. No other animal model has been found, which is why there has become a tacit agreement among researchers within the HIV/AIDS community that it is okay to experiment on human beings. All one need to is look at the dozens of studies that have been done in Third World countries, wherein the idea of informed consent is all but non-existent, and compliance is enforced by mis-and/or dis-information and hyperbole about consequences to the "infected" patient if they fail to use toxic drug therapies or willingly subject themselves to the administration of one or another vaccine. Note that, to date, there are over 60 failed vaccine trials...most of which were perpetrated on subjects in Third World countries.\n\nSecond, and more importantly: according to well-documented evidence supporting this - and manifold statements by Luc Montagnier, himself - so-called HIV has never been successfully isolated, nor have apparently HIV-infected samples been shown to cause any disease in healthy subjects (lab animals or human beings).\n\nThis does not mean there is no such retrovirus; it means that such a virus has not been shown to exist by direct means. That said, the science built upon this failure to isolate is flawed and filled with inconsistencies, regardless of how elegantly complex it has become. What was, we would like to believe, once begun as a scientific investigation, has become a a religious movement; one whose acolytes not only will not engage any longer in applications of scientific methodology but who, at the mere suggestion there might be problems with the HIV=AIDS hypothesis, will seek to publicly crucify and discredit those who question this religious dogma. \n\nWhere is the science in all of this? What has become of The Scientific Method? What has become of intellectual discourse and the questioning of any and all theories? Even after nearly a century since Einstein first described his Special Theory or Relativity, there was open and scholarly scientific debate around this. Yet, a scant three years after the HIV=AIDS hypothesis was first proposed, it became sacrilege to post a scientific objection to this hypothesis, on the merits, and anyone daring to engage in questioning was labeled a "dissident," a "heretic" and/or a "Holocaust deny-er. As early as 1987, anyone in the medical/scientific communities who questioned the HIV=AIDS hypothesis, or who dared to propose an alternative model, was publicly ostracized. Internationally noteworthy careers were destroyed over daring to exercise scientific (and one would argue, healthy) skepticism regarding this hypothesis. At what other time in the course of modern medical and scientific discovery has this been true? \n\nIf the science behind this hypothesis is so solid, what then is there to fear from entertaining opposing perspectives? One can only conclude that the most dogmatic of these "true-believers" recognize that the HIV=AIDS hypothesis is rife with problems, and engaging with anyone who questions their dogma might mean the undoing of what has become a convoluted and incomprehensible pseudo-science (a "New-Age Religion") - one with horrific consequences for the innocents who are being subjected to dangerously toxic drug therapies and equally toxic "vaccines." Worse still, the general public, by and large, has little or no idea of the manner in which they have been duped into participating in this religious crusade.\n\nThis scientist questions the validity of ANY science whose main proponents have ceased questioning their own dogma. There is a fundamental flaw in this hypothesis, and it is high time we all begin to question what he have been led to believe is scientific fact, when indeed it is merely one more religious "truth."\n
Avatar of: anonymous poster

anonymous poster

Posts: 26

March 4, 2009

I appreciate your wonderfully witty response to this otherwise ridiculous article on the pseudoscience of HIV/AIDS. Are you a scientist, as well, or merely a dubious onlooker?\n\nPeace... a concerned scientist.\n\n
Avatar of: Hongrong Cai, MD

Hongrong Cai, MD

Posts: 14

March 4, 2009

Basically it works similarly as a condom, providing a barrier between HIV and the entry, dendritic cell or CD4+ T cell.
Avatar of: anonymous poster

anonymous poster

Posts: 16

March 4, 2009

Well said. However, the success of the RT inhibitors does tend to point to some truth in the HIV=AIDS story. Perhaps HIV causes only a part of the progression to AIDS. Is there some other second or third mode of immune system failure that finalizes the progression to AIDS? Think about the long-term-nonprogressors and the lack of a succesful animal AIDS model.
Avatar of: anonymous poster

anonymous poster

Posts: 26

March 4, 2009

Yes, I'm a molecular developmental biologist... but sometimes too lazy to dig into the real story of what gets posted by TheScientist.com and I've never been very Politically Correct... hence a few irreverant comments. So you're welcome and thanks for noticing.\n\nAs for the HIV/AIDS "controversy" and related conspiracy theories, I think they are based on falacies and that the one "famous" scientist who says HIV is not the cause of AIDS is just being pig-headed. It is very clear that the disease we call AIDS can be transmitted from one person to another by something as simple as a needle-stick accident in a hospital. And, it is quite easy to detect HIV DNA in the T-cells of HIV/AIDS patients, but it is not present in people without the disease. Of course there are some *rare* people with natural immunity or at least resistance, but they are the exception, and not a reason to doubt that the cause of AIDS is HIV.\n\nAnother writer correctly pointed out that the effectiveness of anti-retroviral cocktails in helping most and possibly even curing some patients makes it clear that a retrovirus is responsible, not some mythical environmental toxin or thinking bad thoughts (yes, some New Age people really believe that stuff).\n\nI have a challenge for all the people who are sure HIV isn't necessary and sufficient to cause AIDS. Let's give you an injection of purified HIV and see what happens. We only need a few to several volunteers for it to be statistically significant. Then we'll see how they are doing after a year or two. If they are all fine, I will eat my proverbial hat.\n\nI think there is a reasonably good AIDS model. It is not HIV in chimpanzees... it is SIV in rhesus macaques. Poor things... instead of suffering from AIDS, they should have someone rubbing love-lotion on their privates.\n\nBaxter Zappa

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