EXECUTIVE SUMMARY

The push to increase women’s ability to protect themselves from simultaneous sexual and reproductive health risks, including unintended pregnancy, HIV, and other sexually transmitted infections, continues with the start of a clinical trial of a three-month vaginal ring. The ring is designed to release dapivirine, an antiretroviral drug to prevent HIV, and levonorgestrel, a contraceptive hormone.

  • The study will be conducted at the University of Alabama at Birmingham and Magee-Womens Hospital, a teaching hospital affiliated with the University of Pittsburgh.
  • Other multipurpose technology options in the pipeline include other vaginal rings, gels, and fast-dissolving vaginal inserts and films.

The push to increase women’s ability to protect themselves from simultaneous sexual and reproductive health risks, including HIV, unintended pregnancy, and other sexually transmitted infections, continues with the start of a clinical trial of a three-month vaginal ring.

The ring slowly releases dapivirine, an antiretroviral drug designed to prevent HIV, and levonorgestrel, a contraceptive hormone. Dapivirine, also known as TMC-120, is a non-nucleoside reverse transcriptase inhibitor, which binds to and disables HIV’s reverse transcriptase enzyme, a key protein needed for HIV replication.

The nonprofit research group International Partnership for Microbicides (IPM) has joined Microbicide Trials Network (MTN), funded by the National Institutes of Health, to conduct this study. Researchers will assess the ring’s safety and pharmacokinetics. Results of the trial, including the product’s acceptability to women and their willingness to use it in the future, will be used to guide the ring’s formulation and future research efforts.

Women’s sexual and reproductive health needs do not exist in isolation, and neither should their prevention options, says Zeda Rosenberg, ScD, International Partnership for Microbicides founder and chief executive officer. A long-acting product that gives women two prevention methods in one may be “quite appealing,” she says.

“The only way to end the HIV epidemic is to offer women product options that meet their various needs, and IPM remains committed to making this a reality,” Rosenberg notes. One way to diminish the HIV epidemic is to offer women product options that meet their various needs, Rosenberg offers.

Two U.S. Sites to Conduct Study

The MTN-030/IPM 041 will take place at two sites: The University of Alabama at Birmingham and Magee-Womens Hospital, a teaching hospital affiliated with the University of Pittsburgh.

The Phase I randomized, double-blind study marks the first time a vaginal ring containing a combination of dapivirine and levonorgestrel will be tested in humans.

Researchers will randomly assign 24 healthy women 18-45 years of age who are not pregnant to one of two groups over a 14-day period. Women will use either a vaginal ring containing 200 mg dapivirine and 320 mg levonorgestrel or a ring containing 200 mg dapivirine alone.

All women participating in the study will undergo testing and receive counseling to reduce their risk of acquiring HIV and other sexually transmitted infections, and will be provided male condoms and other health services. Results are expected by mid-2018.

“Many of the women who have participated in our studies have told us that they want a single product that can provide both contraception and HIV prevention,” said Sharon Hillier, PhD, professor and vice-chair for faculty affairs, and director of reproductive infectious disease research, department of obstetrics, gynecology, and reproductive sciences, at the University of Pittsburgh School of Medicine and principal investigator for the research. “We are excited about the next-generation microbicide products that we hope will address that unmet need.”

What researchers will learn from this study will set the course for the future of the dual-purpose dapivirine vaginal ring, according to Sharon Achilles, MD, PhD, MTN-030/IPM 041 protocol chair and a lead investigator at the Magee-Womens Hospital clinical research site.

“If all goes well, we would then proceed to studies involving more women who would use the ring longer, for up to three months, as it was intended,” says Achilles, an assistant professor of obstetrics, gynecology, and reproductive sciences at the University of Pittsburgh School of Medicine and director of the Magee-Womens Research Institute Center for Family Planning Research. “This study is a critical first step on a pathway that we hope will ultimately enable us to provide women with an easy-to-use product that can provide safe and effective, long-acting protection against both HIV and unintended pregnancy.”

In 2016, MTN and IPM research teams reported results of two Phase III efficacy trials of the monthly 25 mg dapivirine vaginal ring, with findings indicating that the vaginal ring could deliver an antiretroviral drug to prevent HIV infection. Data suggested that overall risk of HIV infection was reduced by about 30% across both studies, with higher levels of protection observed in women who used the ring most regularly.1,2

The two trials, MTN’s ASPIRE and IPM’s The Ring Study, investigated 4,588 women in four African countries where HIV rates for women continue to be among the highest in the world. (For more information on this research, please visit: http://bit.ly/2twpOHi.)

Two open-label studies involving former Phase III trial participants in the ASPIRE and Ring investigations are collecting additional safety, adherence, and efficacy data on the monthly dapivirine ring that will help inform its implementation as the ring moves toward potential regulatory approval.

A separate trial (MTN-034/IPM 045) will evaluate safety and adherence of the monthly vaginal ring and daily use of tenofovir as oral pre-exposure prophylaxis among adolescent girls and young women, as well as use in pregnant and breast-feeding women.

More Options in Pipeline

What other possible multipurpose technology (MPT) options are in the research pipeline? The Initiative for Multipurpose Prevention Technologies (IMPT), an international collaboration of researchers, advocates, and funders working together to advance the development and introduction of MPT options, was awarded a $4.5 million grant from the U.S. Agency for International Development in August 2016 to advance research in the field.

“Women worldwide tell us they need more prevention options that they can initiate and that fit the realities of their daily lives,” Bethany Young Holt, PhD, MPH, IMPT director and co-founder, said in a statement accompanying the funding announcement. “The MPT field is committed to prevention approaches that women will want and be able to use.”

There are a handful of MPT products in development at the same Phase I clinical trial stage as IPM’s ring, according to Kathryn Stewart, MPP, IMPT deputy director. These include products that would combine protection against unintended pregnancy/HIV/HSV-2 (herpes), unintended pregnancy/chlamydia/gonorrhea/HIV/HSV-2 (herpes), and HIV/HSV-2 (herpes)/HPV. These methods include vaginal rings, gels, and fast-dissolving vaginal inserts and films. (For more information about all methods now under development, please visit: http://www.theimpt.org.)

A research organization called CONRAD has been developing MPTs to prevent unplanned pregnancies and protect against HIV/AIDS or other STIs. With funding from USAID and the National Institutes of Health, researchers at CONRAD pioneered a screening program designed to identify compounds with dual activity against sperm and HIV.

CONRAD’s levonorgestrel/tenofovir-releasing intravaginal ring is under investigation in a Phase I study at Eastern Virginia Medical School in Norfolk and Profamilia in the Dominican Republic.

Evofem is developing Amphora, a non-hormonal vaginal gel that maintains a low vaginal pH, which creates an unfriendly environment for sperm and bacteria. Amphora uses lactic acid to maintain the acidic pH in the vagina. Its properties could offer many potential advantages for use, either alone or in combination with another active ingredient, such as tenofovir.

Amphora’s potential applications could include use as a microbicidal product, a personal lubricant, or a vaginal contraceptive (alone or with a barrier method).3

REFERENCES

  1. Nel A, van Niekerk N, Kapiga S, et al. Safety and efficacy of a dapivirine vaginal ring for HIV prevention in women. N Engl J Med 2016;375:2133-2143.
  2. Baeten JM, Palanee-Phillips T, Brown ER, et al. Use of a vaginal ring containing dapivirine for HIV-1 prevention in women. N Engl J Med 2016;375:2121-2132.
  3. Bayer LL, Jensen JT. ACIDFORM: A review of the evidence. Contraception 2014;90:11-18.