Science eyes new forms of barrier protection
In 2007, the Centers for Disease Control and Prevention reported that 26% of HIV/AIDS diagnoses among adolescents and adults were among females.1 What will it take to expand the number of available options for female-controlled prevention of infection?
Two scientific groups are examining new forms of barrier protection that can be used by women to fight HIV infection. Researchers at the Infectious Diseases Research Centre at the Université Laval in Québec, Canada, have just published two articles on the recently completed Phase I/II trial of the Invisible Condom.2,3 The candidate microbicide offers a physical barrier in the form of a gel that blocks the entry of pathogens into the mucosa and a chemical barrier, sodium lauryl sulfate (SLS), within the gel that kills sexually transmitted pathogens including HIV.
The Canadian scientists are searching for the funds for the upcoming Phase III trial to be carried out in nearly 5,000 women, says Rabeea Omar, PhD, CCRP, an associate professor at the University and project chief of its Infectious Diseases Research Centre. In its currently published work, investigators report on the results of the randomized, doubled-blind, placebo-controlled study in healthy women from Yaoundé, Cameroon. Scientists enrolled 260 women in the study and randomly assigned them into three study arms: gel alone, gel plus SLS, and placebo gel. Thirty-seven sexually abstinent women applied gel intravaginally once a day for 14 days, while 75, 74, and 74 sexually active women applied gel intravaginally once, twice, or three times daily, respectively, for 14 days.2 Because the Invisible Condom formulations and applicator were found to be comfortable, well tolerated, and acceptable when applied intravaginally, researchers carried out an extended safety study.3 Women applied gel intravaginally twice daily for eight weeks; 194 sexually active women applied placebo (41), polymer alone (76), or polymer/SLS (77). The Invisible Condom gel formulations were well tolerated with no reported serious adverse events.3
Researchers at the University of Utah in Salt Lake City are designing a vaginal gel that blocks HIV by becoming impermeable in response to the pH change induced by the presence of semen. The gel includes a polymer engineered to bind to HIV surface proteins to halt viral transport to susceptible tissues and HIV target cells. The microbicide candidate, dubbed as a "molecular condom," was one of 10 microbicide-related projects named in May 2009 as $100,000 recipients of the Bill & Melinda Gates Foundation's Grand Challenges Explorations grants. The grant program is designed to develop a pipeline of creative scientific ideas that could change the face of global heath.4
Patrick Kiser, PhD, an associate professor of bioengineering at the University of Utah's College of Engineering, and research associates have published early research testing the behavior of the new gel and showing how it traps HIV particles.5 Kiser says his team is working on studying the movement of other viruses, as well as sperm, in these gels. They also are looking at testing the gels in animal models.
In 2006, Kiser and colleagues published a study on their development of another molecular condom candidate. The candidate was designed to be applied vaginally as a liquid, turn into a gel coating at body temperature, and then in the presence of semen, turn into liquid and release an anti-HIV drug.6 When the candidate did not appear to perform as expected, scientists developed the current formulation, which also changes in response to changes in pH in the vagina caused by the introduction of semen during sex. However, unlike the old gel, which became liquid at the higher pH of semen, the new candidate forms into a semisolid at the pH of semen, creating a mesh of cross-linked molecules.
The new gel is applied as a gel, then becomes more solid and impenetrable as changes in pH alter the strength of the bond between the gel's two key components. These components are polymers — long, chain-like molecules made of many smaller, repeating units of phenylboronic acid and salicylhydroxamic acid. Scientists also plan to examine the gel's possible use as a contraceptive, as well as its effectiveness against herpes and human papillomavirus.
"My whole lab is devoted to developing new biomedical technologies that are controlled by women to control their reproductive health," says Kiser.
References
- Centers for Disease Control and Prevention. HIV/AIDS in the United States. Fact sheet. Accessed at www.cdc.gov/hiv/resources/factsheets/us.htm.
- Mbopi-Keou F-X, Trottier S, Omar RF, et al. A randomized, double-blind, placebo-controlled safety and acceptability study of two Invisible Condom® formulations in women from Cameroon. Contraception 2009. DOI:10.1016/j.contraception. 2009.03.020.
- Mbopi-Keou F-X, Trottier S, Omar RF, et al. A randomized, double-blind, placebo-controlled Phase II extended safety study of two Invisible Condom® formulations in Cameroonian women. Contraception 2009. DOI: 10.1016/j.contraception.2009. 07.002.
- Alliance for Microbicide Development. Gates Foundation Announces Awardees of Grand Challenges Explorations Grants. News alert. Accessed at www.microbicide.org/cs/news_alert_detail?pressrelease.id=312.
- Jay JI, Shukair S, Langheinrich K, et al. Modulation of viscoelasticity and HIV transport as a function of pH in a reversibly crosslinked hydrogel. Advanced Functional Materials 2009; DOI: 10.1002/adfm.200900757.
- Gupta KM, Barnes SR, Tangaro RA, et al. Temperature and pH sensitive hydrogels: An approach towards smart semen-triggered vaginal microbicidal vehicles. J Pharm Sci 2007; 96:670-681.
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