New Hopes for Pring
The success of anti-retroviral (抑止肿瘤病毒) drugs in treating HIV is getting researchers at the 16th International conference excited at the prospect that the potent medicines might be exploited to perform double duty. Why not use the power of these ARVs to pr an HIV transmission or infection from taking hold in the first place Bill and Melinda Gates asked that provocative question on the opening day of the conference, and are committing their considerable financial resources toward finding an answer. In their remarks, they highlighted the need to develop microbicides and oral-prion drugs while we wait for a vaccine. And they will get their first hint at how smart their decision was this Thursday, when scientists from West Africa report the initial results from the first trial studying an oral prion drug.
So how realistic are the Gates in expecting even more from the ARVs "I do think the range of prion options we have within the next decade will greatly expand," says Dr. Helene Gayle, President of Care USA and co-chair of the conference. "The biologic plausibility for both microbicides and oral-prion drags is so great." Dr. Mark Dybul, U.S. Global Coordinator, said that if a microbicide or prion drug becomes available to protect people from infections, they would be funded under the President’s Emergency Plan for Relief if countries chose to use them. "We would support all of that; it would be perfectly within our mandate to do all that," he told TIME.
Pring HIV is the only way to keep the number of new infections that occur each year -- 4 million -- from growing. And yet prion strategies, always the ugly stepsister to treatment programs, have not really taken hold in the developing nations where the rate of infection is highest. An effective vaccine, of course, is the ultimate prion weapon, but as the Gates’ pointed out, an HIV shot is still a long way off. In the meantime, microbicides could be one way to co-opt ARVs into the prion war; these are chemical compounds, usually in the form of a gel or cream, that women can use vaginally prior to intercourse to stop the transmission of HIV -- it’s the same idea behind spermicides (杀精子剂), which are chemical barriers to sperm entering the vagina and causing pregnancy. It’s an elegantly approach, made even r by the fact that researchers didn’t really have to start from scratch to come up with new anti-HIV compounds; they already have them in the ARVs, which now interrupt the virus from infecting cells at various points in its life cycle.
The key difference is that in a microbicide, the drugs are being used in healthy people rather than in those infected with HIV. When ARVs are used for treatment, both doctors and patients are willing to tolerate a higher level of side effects -- after all, if the choice is between dying from HIV- and side effects, most patients opt for the latter. If the drugs are to be used to pr infection, however, everything changes; understandably, healthy people aren’t as likely to accept the same level of side effects and toxicities as those already infected.
That’s why clinical trials are so significant. So far, there are 30 to 40 different microbicide candidates being tested in animals, and five trials in Ghana, Nigeria and other developing nations at the most advanced stages of testing in women. Dr. Gita Ramjee, of the HIV Prion Research Unit in D, South Africa, has worked with all five, and is hopeful that they will prove effective and make an impact on the disease. Because these latest microbicides are reformulated ARVs, however, the problem of the virus becoming resistant to them is a potential drawback. Dr. Peter Plot, of UN, suggests basing microbicides only on the drugs do not make it through the pharmaceutical pipeline many are rejected because they don’t maintain high enough levels in the blood to treat an HIV infection, but could be sufficiently powerful to pr transmission.
But Zeda Rosenberg, CEO of International Partnership for Microbicides, which has sponsored a number of the trims, believes that since microbicides aren’t designed to enter the bloodstream and suppress HIV there, resistance won’t be as huge a hurdle as it is for ARVs used in treatment. "The studies so far, with most of the ARV products, suggest very low levels of systemic absorption," she says. "It may be that there is insufficient absorption to select for resistance. But we won’t know that answer until we do the efficacy trials." The first of these results, from Nigeria, will be released in September 2007. Even if they prove to be effective, Ramjee and others stress that microbicides -- whether they come in the form of a gel or cream applied before intercourse, or as part of a delayed release ring inserted into the cervix that can provide the drug for anywhere from 30 to 90 days -- are not a physical barrier to HIV. At best, microbicides may be 80% effective in pring the transmission of the virus during intercourse. To improve the chances that the virus doesn’t slip by, however, there is always the possibility of combining the ARVs, in the same Way that doctors currently do to treat infected patients.
On the ground, however, Ramjee noted that it’s sometimes hard to keep patients enrolled. Not only do women often face opposition from their male partners to using the microbicide, there is the reality that many of the women enrolled end up getting pregnant, and as a result, have to drop out. (The trial sponsors, including USAID, NIIH and the Gates Foundation, do continue to provide family planning and other pre and post natal services to these women, if they choose to use them. )
Even more tantalizing (让人着急的) than the microbicides is the idea of taking a pill before intercourse or other high-risk behavior, and thereby becoming protected from HIV. Drugs for pre-exposure prophylaxis (PrEPs = Prion of or protective treatment for disease) were born from the success of programs that pr mother-to-child transmission; since ARVs given to women pre-and-post-delivery are effective in reducing the transmission of HIV to the child, and using ARVs before exposure to HIV have the same effect in protecting partners. Five trials, all involving two compounds, Tenofovir or Truvada, are now underway in Thailand, Botswana, Peru, West Africa and even the U.S. It’s being tested in groups at highest risk of transmitting the virus-commercial workers and gay men. "What you want is a high level of ARV in the blood and body secretions, so that when you are exposed to HIV, the ARV will kill the virus," explains Dr. Peter Plot, director of UN. "Because at infection, the number of virus particles is very, very small, so you can inhibit or kill them before they penetrate cells or just at the early phases of infection."
Piot, however, notes that if PrEPs prove effective, they will create a number of thorny ethical issues: How will use of the drug be monitored Could it become a "party" drug or a Viagra-like crutch that people erroneously believe will provide them with absolute protection "We’ll need a lot of behavioral research, which I think should be initiated as soon as possible," he says. "Particularly when it looks like PrEP will become a reality." Resistance is a key issue with PrEP as well, and if effective PrEP drugs are used widely, the problem of resistant HIV expands rapidly. "We need to be better about looking at what public health strategy we should use for ARVs," says Gayle. "There are a lot of potential pitfalls, but our commitment has to be to make options available, develop options that are safe and effective, so they can be used by people who need them the most, and at the same time make sure we have policies so they are used in the safest way possible from a public health perspective.\
Lack of prion strategies and treatment programs makes the developing countries the largest in the number of HIV infection.