Of microbicides & vaccines.

The more you read about women and HIV, the more depressing it can get. But there is hope on the horizon--closer than you might expect. While HIV vaccines have garnered most of the attention and funding, a more realistic preventive approach for women is microbicides, "chemical condoms" that sabotage the virus.

"While condoms are excellent (at preventing the virus from infecting another person), it's often difficult for women to negotiate the use of condoms," says Betsy C. Herold, MD, professor of pediatrics and microbiology at Mount Sinai School of Medicine in New York and a leading researcher on the use of microbicides to prevent HIV. "It's imperative that there be alternative strategies available to women for their own health."

Enter microbicides. The microbicide is a substance that will either kill or reduce the infectivity of the virus. Microbicides could be infused into sponges, formed into time-release suppositories or developed as intravaginal rings that work for weeks or months.

Microbicides come with an added bonus: Many are also effective against other sexually transmitted infections, including herpes, chlamydia and gonorrhea. (11)

Today, five microbicides are being tested in six late-stage clinical trials involving tens of thousands of women in the United States and developing countries. Some work by disrupting the viral envelope, blocking the virus's entry into cells or making the vagina itself hostile to the virus, while others disrupt the virus's life cycle.

The trials are expected to wrap up in 2007 at the earliest, says Dr. Herold, at which time the U.S. Food and Drug Administration will consider their approval.

While microbicides show great promise, safety is a major concern. Studies found that one microbicide thought to protect against HIV--nonoxynol-9--actually increased the risk of transmission, because it irritated the lining of the vagina.

Once one or more microbicides are approved, Dr. Herold predicts that future research will focus on developing combination microbicides, "so we can hit the virus at several different steps." This would also help prevent the virus from becoming drug resistant.

"The concept of vaccines is very exciting, and they are our greatest hope for HIV prevention in the long term, but they have a long way to go in their development," Dr. Herold says. One challenge is that the virus attacks the immune response, yet vaccines rely on a strong immune response to prevent infection--a kind of medical catch-22. Another challenge is that the virus is constantly changing. Developing a vaccine that will work long term is like trying to hit a moving target.

Nonetheless, the National Institutes of Health has initiated or conducted more than 75 clinical trials of more than 35 vaccines. Ten new vaccines entered clinical trials in the past two years and six to eight are expected to begin testing within the next 18 months. (12)

However, despite almost twenty years of research and more than $500 million spent in recent years on vaccine research (compared to about $52 million a year for microbicidal research), (13) a safe and effective vaccine is not likely to be available for at least another five to 10 years, she predicts.

References

11 Madan RP, Keller MJ, Herold BC, Prioritizing prevention of HIV and sexually transmitted infections: first-generation vaginal microbicides. Curr Opin Infect Dis. 2006 Feb;19(1):49-54. Review.

12 Vaccines. NIH fiscal year 2007 plan for HIV-related research. Available at: http://www.nih.gov/od.

13 Office of AIDS Research, National Institutes of Health, US Dept of Health and Human Services. FY2005 budget. www.nih.gov/od.

RELATED ARTICLE: HIV/AIDS Glossary

* Antiretroviral: A drug that suppresses the activity or replication of retroviruses such as HIV by interfering with various stages of the viral life cycle.

* Acquired Immunodeficiency Syndrome (AIDS): A disease of the body's immune system caused by the human immunodeficiency virus (HIV). AIDS is characterized by the death of CD4 cells (an important part of the body's immune system), which leaves the body vulnerable to life-threatening conditions such as infections and cancers.

* AZT (zidovudine): Sold under the brand name Retrovir, a drug approved for use as part of combination antiretroviral therapy to treat HIV disease.

* HAART: Highly active antiretroviral therapy. Combinations of drugs people with HIV take to control the virus.

* Human Immunodeficiency Virus (HIV): The virus that causes Acquired Immunodeficiency Syndrome (AIDS).

* Microbicide: An agent that inactivates, kills or destroys microbes like viruses.

* T cell: A disease-fighting white blood cell, including CD4 and CD8 cells. HIV infects and kills CD4 cells, weakening the immune system. The number of CD4 cells in a blood sample indicates the health of the immune system.

* Viral load: The amount of viral genetic material in the blood or other tissues, often expressed as number of copies per milliliter (mL).