New Approaches to Preventing HIV
Vaginal ring containing antiviral drug for 30-day continuous delivery.
The spread of HIV (human immunodeficiency virus) is growing at a staggering rate of about 15,000 new infections each day globally. Although currently more men have HIV than women worldwide, the rate of infection is higher among women, who may soon outnumber men with HIV, according to the Centers for Disease Control and Prevention. HIV can develop into the deadly AIDS (acquired immunodeficiency syndrome).
The majority of new HIV infections occur through heterosexual intercourse, and therefore, targeting the growth of HIV infection among women will also slow the growth of infection in men. To that end, Dr. Patrick F. Kiser, an assistant professor in the Department of Bioengineering, is seeking to develop new drug delivery systems for women, called vaginal microbicides, that work as antiviral agents to block HIV infection before it can take hold in the female body.
"The idea behind microbicides is simple," says Dr. Kiser. "Apply a protective material the vagina prior to intercourse which will block infection by HIV at any step in the infection process and viral life cycle."
Unfortunately, he says, the simplicity ends there. The challenges of effectively using antiviral drugs include the complexity of the mechanisms of HIV infection, the difficulty of determining the optimal properties of microbicides--whether the drug should be released continuously or in a big burst, depending on the type of inhibitor that should be used--and and the potential presence of other viruses that may increase a woman's risk of HIV infection.
Dr. Kiser and his associates are testing different ways of delivering the microbicide's valuable antiviral properties through the application of gels and vaginal rings that release the antiviral agent over time, or quickly when they come in contact with the virus.
"Many research groups focus their efforts on active agents," he says. "However, we are among the first to leverage the body of research on bioresponsive delivery systems to the important problem of changing the action of HIV on human genital tissue."
One method of antiviral delivery that is being tested by Dr. Kiser involves applying an HIV inhibitor (reverse transcriptase inhibitor--or RTI) to the genital tissue, where it crosses into the vaginal wall preparing the tissue in case of an HIV attack. Several gels and vaginal rings containing RTI are currently under development or in clinical trials.
Another method involves coating the walls of the vagina with a protective microbicide barrier so that the virus is unable to penetrate the vaginal wall, while a third method involves attacking the virus in the semen before it can penetrate vaginal cells.
Combining the last two methods, Dr. Kiser is developing new 'smart' technology that creates a physical and chemical barrier to the virus. Called a "molecular condom," this antiviral liquid is released through a vaginal ring inside a woman's body and forms a protective gel that coats the vaginal walls. During intercourse, the protective barrier releases antivirals into semen to attack a potential virus before it can reach vaginal tissue. The release of the microbicide is triggered both by an enzyme in semen, called protease, and by normal changes to pH levels in the vagina that occur when contacted with semen. The release of the microbicide neutralizes the virus before it can infect vaginal cells.
Other related research in Dr. Kiser's lab includes new intravaginal rings that are customized to deliver a variety of antiviral agents for 30 days. "We believe this new technology is going to be a successful way of delivering antiviral agents because they are easy to use and women like using them. There is also the possibility of covert use where a woman's partner does not know that an antiviral agent is being used," he says.
Although no microbicidal products are approved for use on the market yet, several different first generation-candidate microbicides are being tested in Phase III clinical trials. "Its just a matter of time before they can be made available to women as an important weapon in combating the global HIV pandemic," says Dr. Kiser.
Dr. Patrick F. Kiser is an assistant professor in the Department of Bioengineering. His current research focuses on the development of microbicides--novel drug-delivery technologies that aim to prevent the transmission of HIV and other sexually transmitted diseases. Dr. Kiser also studies various methods of drug delivery, formulations technology, and advanced materials for biological applications.
After working in private industry on biomedical and chemistry development and research for several years, he came to the University of Utah in 2002 to start his independent research career.
Prior to obtaining a doctorate from Duke University, Dr. Kiser worked on numerous projects including coating small microgel particles with lipid bilayers, studying the properties of hydrogel microspheres, and designing and testing a novel set of bioerodible crosslinkers.
Dr. Kiser also holds a bachelor's degree in chemistry and a master's degree in organic chemistry from the University of Wisconsin. For more information on Dr. Kiser's research, visit his web page.