Multipurpose methods show research advances
EXECUTIVE SUMMARY
Strides are being made in development of multipurpose prevention technologies, defined as a single product or strategy configured for at least two sexual and reproductive health prevention indications: unintended pregnancy, HIV, and other sexually transmitted infections.
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Investigators at CONRAD are testing an intravaginal ring that can offer a sustained 90-day codelivery of tenofovir, an anti-HIV drug, and levonorgestrel, a contraceptive.
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Population Council scientists are developing a dual-protection gel, as well as an intravaginal ring, for women that combines levonorgestrel with two antiviral agents: MIV-150 and zinc acetate. The International Partnership for Microbicides is developing a 60-day intravaginal ring that combines the antiviral agent dapivirine with levonorgestrel.
Consider these statistics: In 2010, 1.8 million people died of AIDS, and in 2009, an estimated 2.6 million became infected with HIV.1 Each day, about 500,000 young people, mostly women, contract an sexually transmitted infection (STI).2 Globally, 222 million women have an unmet need for modern contraception.3 In the United States, nearly half of all pregnancies among American women are unintended, and four in 10 of such pregnancies end in abortion.4 Of the 18.9 million new cases of STIs each year in the United States, 9.1 million (48%) occur among 15-24 year olds.5
Scientists are working on development of multipurpose prevention technologies (MPTs) to combat such problems. As defined, MPTs are a single product or strategy, configured for at least two sexual and reproductive health prevention indications: unintended pregnancy, HIV, and other STIs, says Bethany Young Holt, PhD, MPH, executive director of the Northern California-based Coalition Advancing Multipurpose Innovations (CAMI), part of the Public Health Institute. Holt discussed MPT development at the recent Reproductive Health 2013 conference in Denver.6
Why develop MPTs? According to Holt, there are two reasons:
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gain greater efficiency in terms of cost, access, and delivery of sexual and reproductive health prevention products;
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capitalize on the demand in populations using one product type to achieve uptake and use of a second "product."
Data emerges on ring
Early research conducted by CONRAD, an Arlington, VA-based nonprofit reproductive health and HIV prevention organization, is aimed at development of an intravaginal ring that can offer a sustained 90-day codelivery of tenofovir, an anti-HIV drug, and levonorgestrel, a contraceptive. Preclinical data on the ring was presented at the November 2013 American Association of Pharmaceutical Scientists Annual Meeting and Exposition in San Antonio.7
Working with researchers from the University of Utah, CONRAD scientists designed the ring using reservoir-type polyurethane segments. The segments were individually optimized to deliver each drug at the desired dosage. Investigators performed in vitro release testing and three-month pharmacokinetic studies of the ring in rabbits and sheep, and they compared drug levels to those seen with use of tenofovir gel. The pharmacokinetic studies found that levels of tenofovir in the target tissue delivered from the ring are similar or higher than those obtained after tenofovir 1% gel application. Tenofovir 1% gel application is a product that has proven to be effective in preventing HIV and herpes simplex virus (HSV) infections in women. Release of the contraceptive agent also was consistent with previous levels tested to be efficacious in women, data indicate.
Phase I studies are planned for early 2014 in women, says Annette Larkin, CONRAD spokesperson.
New combinations eyed
The New York City-based Population Council also is developing MPTs that combine antiviral and contraceptive ingredients into one product for on-demand or long-term use. Population Council scientists are developing a dual-protection gel for women that combines levonorgestrel as the contraceptive agent, with two antiviral agents, MIV-150 and zinc acetate. MIV-150 is an enzyme inhibitor developed by Medivir in Stockholm, Sweden, that prevents HIV-infected cells from producing new virus, while zinc acetate is an antiviral agent with activity against HIV and HSV. The Population Council also is developing an intravaginal ring using the same drug combination for long-term use.
The Silver Spring, MD-based International Partnership for Microbicides is developing a 60-day intravaginal ring which combines the antiviral agent dapivirine with the contraceptive agent levonorgestrel to protect against HIV as well as unintended pregnancy. It plans to begin a Phase I trial in 2015.
New gel to be combined with diaphragm
In another MPT approach, CONRAD scientists are reformulating tenofovir 1% gel by adding sperm-immobilizing agents. This new gel will be combined with the SILCS diaphragm, a single-size barrier device that fits most women. (To read more about the barrier device, see the Contraceptive Technology Update article, "New data emerges on one-size diaphragm," December 2011, p. 139.)
If testing in animals shows efficacy and no safety concerns are identified, CONRAD plans to test the gel and device combination in two clinical trials. The first will be a postcoital test that will look at the ability of the duo to immobilize sperm, followed by a safety and pharmacokinetic/pharmacodynamic study to check for safe use and measure levels of tenofovir in the vagina and plasma.
References
- UNAIDS. Global Report: UNAIDS Summary of the AIDS Epidemic, 2010. Available at http://bit.ly/18DECWD.
- United Nations Population Fund. Reproductive Health: Breaking the Cycle of Sexually Transmitted Infections, 2009. Available at http://bit.ly/1fkWVla.
- Singh S, Darroch JE. Adding It Up: Costs and Benefits of Contraceptive Services — Estimates for 2012. New York: Guttmacher Institute and United Nations Population Fund; 2012.
- Finer LB, Zolna MR. Unintended pregnancy in the United States: incidence and disparities, 2006. Contraception 2011; 84(5):478-485.
- Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2009. Atlanta: Department of Health and Human Services; 2010.
- Holt BY. Multipurpose prevention technologies (MPTs) for sexual and reproductive health. Presented at the Reproductive Health 2013 conference. Denver; September 2013.
- Kiser P, Clark M, Clark J, et al. Development and pharmacokinetics of a 90-day intravaginal ring for the sustained co-delivery of the microbicide tenofovir and contraceptive levonorgestrel. Presented at the American Association of Pharmaceutical Scientists (AAPS) Annual Meeting and Exposition. San Antonio; November 2013.
