A Novel Strategy Against Sexually Transmitted Infections
by Jeffrey Laurence, M.D.
February 16, 2006—People in the United States are three times as likely as people living in any other resource-rich nation to die prematurely as the result of sexual activity.
The U.S. Centers for Disease Control and Prevention estimates that about two million people in the U.S. each year have their lives shortened due to illnesses related to sexually acquired genital herpes, human papillomavirus (HPV, the cause of cervical cancer), and HIV. And women are the most seriously affected.
In terms of HIV, one hears much about the "feminization" of the epidemic worldwide. This is tragic, and the focus is usually on the developing world. But the problem is also quite close to home: the proportion of total cases of HIV among women in the U.S. is increasing faster than for any other country in the world.
Some sexually transmitted infections, or STIs, may themselves be of little consequence to overall health, yet can facilitate the transmission of HIV. For example, genital herpes more than triples a person’s risk of acquiring HIV.
These STIs are all theoretically preventable. But abstinence or condom use is often not possible, given social and religious barriers, rape, and the disturbing fact that the major risk factor for HIV transmission to women in many countries is marriage.
Prevention in a pill would be useful; clinical trials are underway with anti-HIV drugs such as tenofovir, though concerns about an increase in HIV drug resistance are real. A locally applied microbicide is also needed.
In an article in a January 2006 issue of the prestigious journal Nature, an amfAR-funded scholar, Dr. Deborah Palliser, from the Department of Pediatrics at Harvard Medical School, describes a novel type of anti-STI microbicide. Working under the mentorship of Dr. Judy Lieberman, a long-standing member of amfAR's Scientific Advisory Committee, Dr. Palliser explored a technique known as "gene silencing."
Gene silencing is a natural defense mechanism used by cells throughout the plant and animal kingdom to suppress the activity of unwanted genes. Taking a clue from nature, scientists have been designing such genetic material, known as small interfering RNAs or siRNAs, to target many things. Dr. Palliser chose to target the genes of genital herpes, HSV-2.
Using a mouse model, Dr. Palliser showed that vaginal administration of an anti-herpes siRNA mixed with fat (lipid) was efficiently absorbed by vaginal and cervical lining cells. It protected most mice from a lethal HSV-2 infection when given before or within a few hours after exposure to the virus. The siRNA had no side effects, and was detectable in genital tissues for at least nine days. Though this technique is still many years away from being used on humans, the estimated current cost for a human dose of such an agent was $8. This cost might be expected to decrease markedly with mass production.
Other scientists have performed test tube experiments to illustrate the promise of siRNAs against HIV itself. And one measure of a promising clinical breakthrough is its appearance in the pages of The New England Journal of Medicine. An article on this subject was written by one of amfAR's research stars, Dr. Ruth Ruprecht. We look forward to presenting future updates on this research.
Dr. Laurence is senior scientific consultant for programs at amfAR.