Antiretroviral (ARV) drugs have transformed HIV infection from a death sentence to a manageable chronic illness for millions worldwide. Now, scientists are testing whether ARVs can be used as microbicides, taken orally or applied vaginally as a gel or foam to prevent the transmission of the AIDS-causing human immunodeficiency virus.

If ARVs are proved as effective as microbicides, they have the potential to dramatically curb HIV infection rates. This is especially true in sub-Saharan Africa where women, who comprise nearly 61 percent of the adults living with HIV there, are eager for products besides condoms that they can use to protect themselves against the disease.

"I think it is very exciting to be integrating microbicides with drugs that have proven to work for treatment," says Roberta Black, chief of the Microbicide Research Branch at the National Institute for Allergy and Infectious Disease (NIAID) in Bethesda, Md. "This really jump-starts research efforts."

Microbicide research is at a crossroads as scientists begin testing the next generation of these drugs in the wake of a series of high-profile failures, including three late-stage clinical trials that were halted in the past year because the tested drug was found to be ineffective and, in one case, actually raised the risk of HIV transmission.

The latter trial, involving nearly 1,400 women in Durban, South Africa; Kampala, Uganda; Cotonou, Benin; Chennai, India; and Karnataka, India, was stopped last year when researchers realized the microbicide gel, made up of cellulose sulfate, not only failed to prevent HIV infection, but upped participants' risk of acquiring the virus. Forty-one women contracted HIV during the trial—25 in the cellulose sulfate gel group and 16 in the placebo gel group.

Carraguard, a seaweed-based microbicide tested by the Population Council, a nonprofit biomedical research group based in New York City, failed to show efficacy in a study carried out between 2004 and 2007 on 6,200 women. Carraguard is a polyanion, meaning that it carries a negative electrical charge that attracts HIV, whose surface is positively charged. The idea was that polyanions could prevent the virus from attaching to the host cell.

Almost simultaneously, last February in the U.K., the Microbicides Development Programme at Imperial College London announced that it was stopping one arm of a trial of another polyanion, PRO-2000, because the product was unlikely to show any benefit.

Two other compounds that showed early promise—nonoxynol-9 and Savvy—have also proved lackluster in recent years. Both are detergents, common agents used in spermicides, that disrupt HIV in test tubes, but in human microbicide trials they did not stop HIV transmission.

"It’s very easy to get depressed," says Polly Harrison, founder and director of the Alliance for Microbicide Development, a Silver Spring, Md.–based nonprofit that advocates for the worldwide development of the products. "But the field has rallied and dusted itself off."

The reason for the rally isARVs. Two classes are in development as microbicides: entry inhibitors that prevent the virus from attaching to target cell surfaces or stop it from entering the cell after attachment, and reverse transcriptase inhibitors (RTIs) that block virus from replicating itself if it succeeds in entering a cell.

7 Comments

1. 1. JimPickett 08:52 AM 12/1/08

   On this World AIDS Day --- I am saddened once again to have a major article on microbicides published in an important publication --- that negates, denies, ignores and silences gay men, other men who have sex with men, and the pressing need for rectal microbicides for both women and men.
   
   And it is troubling to see the term microbicide as being something only applied vaginally to protect against HIV. This is very narrow, and therefore, incorrect. Microbicides are being studied for both vaginal AND rectal application - to protect during vaginal intercourse as well as anal intercourse.
   
   Men who have sex with men around the world are 19x more likely to be HIV+ in comparison to the general population. Do they not deserve a mention as being an important population who could benefit from microbicides? Millions and millions of men are already infected, and many millions more are at risk.
   
   There is a significant amount of research dedicated to the development of safe, EFFECTIVE, and acceptable rectal microbicides. Considering unprotected anal intercourse is a common behavior among HUMANS (women included), and considering that it is much more efficient at transmitting HIV compared to unprotected vaginal intercourse (5 to 80 times more so), does it not deserve a couple of words in this article?
   
   To learn more about rectal microbicides - including scientific endeavors and advocacy efforts - please visit the home of IRMA - International Rectal Microbicide Adocates - http://www.rectalmicrobicides.org
   
   Thank you,
   Jim Pickett, IRMA Chair
   
   

   Reply | Report Abuse | Link to this

2. 2. hotblack 11:02 AM 12/1/08

   Jim, in the eyes of much of this country, HIV is "gods way of punishing homosexuality." I understand not wanting to see real issues as well as your organizations good work sidestepped, but you could also be glad to see articles that make clear that it's not a "gay" a problem. Not that I'd expect to see those people reading articles on a science website, but....
   
   I think it's interesting, though, that those religious radicals wound up coincidentally close to the mark. Diseases aren't Gods way of punishing groups of people whose behavior it doesn't like, they're Natures way of keeping populations in check. Every year, it becomes clearer and clearer that the most critical problems we face stem from overpopulation, and as our population happily spirals out of whack unsustainably, (thanks in no small part to those very same religions urging uncontrolled breeding) HIV performs a definite biological function. With the big picture in mind, it is even more unfortunate that homosexual couples are suffering from HIV, as it's been shown over the years that homosexuality is an effect of, and part of the solution to overpopulation.

   Reply | Report Abuse | Link to this

3. 3. JimPickett in reply to hotblack 06:30 PM 12/1/08

   Gay men, and other men who have sex with men, are in fact, on average, 19 times more likely to be HIV positive compared to the general population ---- a GLOBAL statistic. It is not only a "gay" problem, but HIV among gay men and other men who have sex with men has, sadly, been silenced, denied and negated in much of the world. And millions are dying because of it.
   
   See http://irma-rectalmicrobicides.blogspot.com/2008/11/oh-humanity.html
   
   See http://irma-rectalmicrobicides.blogspot.com/2008/08/piot-rails-against-homophobia-at-aids.html
   
   See http://irma-rectalmicrobicides.blogspot.com/2008/08/global-aids-prevention-gives-short.html

   Reply | Report Abuse | Link to this

4. 4. Daffyd Thomas in reply to hotblack 09:47 AM 12/2/08

   Hot Black, you really need to provide some evidence for this outrageous statement: "in the eyes of much of this country, HIV is "gods way of punishing homosexuality." Which country are you talking about? How many is much? A majority? It would be great to know where you get your information or is it just your opinion?

   Reply | Report Abuse | Link to this

5. 5. theophys 10:32 AM 12/2/08

   It is true that a significant number of Americans view homosexuality as a sin deserving punishment like AIDs. I wouldn't say the majority, but enough to make a difference. I've been to almost every state in this nation and I have found anti-homosexuality sentiments almost everywhere (not always from radicals, not always from conservatives). I think it good that the scientific community doesn't advertise their work towards helping gay men with AIDs. The sad truth is that scientific research requires funding, and taking on something like HIV requires emense funding the likes of which can only come from governements and very wealthy philanthropists. It would be best for everyone if the controversy associated with homosexuality were kept at the edge of the disscussion. Once we find effective treatments and possibly cures or vacines, we can take that knowledge and apply it to homosexual men. It's not that we don't care about the gay men of the world, it's that the best way to help them is to approach the problem with minimal participation from them.

   Reply | Report Abuse | Link to this

6. 6. jpuah23 01:32 PM 12/7/09

   There are many natural ways to rid your body of HIV. In contrast with the traditional antiviral cocktails of medicine today, which cost thousands, have severe side effects, and comes with the double edged sword delema,meaning if the virus doesn’t kill you the cocktails will, this medicine is all natural.Please visit this site for the full information about this subject……http://pushgood-nomorehiv.blogspot.com/

   Reply | Report Abuse | Link to this

7. 7. rachell32skeith 06:24 PM 3/23/10

   hi ! thanks for sharing this informative post.
   
   http://simplestdtesting.com/resources

   Reply | Report Abuse | Link to this