By Rebecca Bowers

EXECUTIVE SUMMARY

Researchers are evaluating a vaginal ring designed to protect women against both HIV and herpes simplex virus type 2 in a Phase I study. The trial is being conducted by researchers from the National Institutes of Health-funded Microbicide Trials Network at three U.S. sites in Alabama, California, and Pennsylvania.

  • Each flexible polymer ring contains 1.4 g of tenofovir, an anti-HIV drug. The ring is designed to release an approximate 10-mg daily dose. The trial will be analyzing the safety of three months of continuous use.
  • Researchers hope the tenofovir ring will be acceptable for use for HIV prevention. While a similar tenofovir gel product was found to be safe, not all women were receptive to using it.

Researchers are evaluating a vaginal ring designed to protect women against both HIV and herpes simplex virus type 2 (HSV-2) in a Phase I study. The trial is being conducted by researchers from the National Institutes of Health-funded Microbicide Trials Network (MTN) at three U.S. sites in Alabama, California, and Pennsylvania.

Each flexible polymer ring contains 1.4 g of tenofovir, an anti-HIV drug. The ring is designed to release an approximate 10-mg daily dose. The trial will be analyzing the safety of three months of continuous use.

To conduct the MTN-038 study, scientists plan to enroll about 50 healthy, HIV-negative participants who will be assigned to using either the tenofovir vaginal ring or a placebo ring for 90 consecutive days, including during menstrual periods. Investigators will conduct medical and laboratory tests to determine the safety of the ring. Participants will be questioned about ring use, what they liked or disliked about it, and whether ring use interfered with sex. Results are projected to be available sometime in mid-2020.

Arlington, VA-based research group CONRAD is providing both the active tenofovir ring and placebo ring products for the study, as well as providing advisory information for the trial. Funding supporters include the U.S. Agency for International Development/U.S. President’s Emergency Plan for AIDS Relief.

“In order to increase uptake and adherence, women need combination HIV/HSV prevention products that fit into their lifestyles,” says Gustavo Doncel, MD, PhD, CONRAD’s scientific and executive director. “We believe the 90-day tenofovir vaginal ring formulation will be much easier and more convenient to use than its vaginal gel counterpart, and hope that through continued clinical development, it becomes a new effective and safe option for women.”

The International Partnership for Microbicides is seeking U.S. and global regulatory approval of a 25-mg dapivirine vaginal ring. If it is approved, the monthly dapivirine ring would be the first biomedical HIV prevention method developed specifically for women. (Contraceptive Technology Update reported on the dapivirine ring; see the January 2019 article, “Researchers Release Initial Results on Developmental Vaginal Ring,” https://bit.ly/2RXzuGs.)

Moving Science Forward

The MTN-038 trial is one of two studies evaluating 90-day use of the tenofovir ring. Earlier studies looked at rings worn by women for an average of 15 days. No safety concerns were observed during these initial studies, with results indicating the ring could deliver enough of the drug to be protective against both HIV and HSV-2.1

CONRAD developed the 90-day tenofovir ring in collaboration with the University of Utah and Northwestern University. It also developed a combination tenofovir/levonorgestrel ring designed to protect against unintended pregnancy, HIV, and HSV. Both products are being evaluated by CONRAD and partners, including the Centers for Disease Control and Prevention, in an expanded safety and acceptability study based in Kenya. CONRAD holds a license from Gilead Sciences Inc. to develop tenofovir-based products for women.

Evaluating Tenofovir’s Promise

Researchers hope the tenofovir ring will be acceptable for use for HIV prevention. A vaginal gel, also developed by CONRAD, underwent extensive testing, with large-scale trials conducted in Africa. Although the gel product was found to be safe, not all women were receptive to using it.2

No product can be effective if it is not used consistently, which was a challenge for women in previous studies, says MTN Principal Investigator Sharon Hillier, PhD, professor and vice chair of the Department of Obstetrics, Gynecology and Reproductive Sciences at the University of Pittsburgh School of Medicine and Magee-Womens Research Institute.

“Women need a range of options that will work within the context of their lives — products that they can and are willing to use,” said Hillier in a press statement. “Many women, we have learned, say that a longer-acting product, like a vaginal ring, would be an attractive option.”

Scientists are looking forward to further testing the ability of tenofovir to protect against HSV-2. Such preventive action was detected during testing of vaginal gel in HIV prevention trials.

“A product that offers protection against both HIV and HSV-2 could have an important public health impact, but first we need to establish that the tenofovir vaginal ring is safe and acceptable when used for 90 days,” says Albert Liu, MD, MTN-038 protocol chair and study director of clinical research at the Bridge HIV Clinical Research Site, San Francisco Department of Public Health, one of the three sites conducting the study. “We hope to answer these and other key questions in the MTN-038 study so that later-phase effectiveness studies might follow.”

REFERENCES

  1. Thurman AR, Schwartz JL, Brache V, et al. Randomized, placebo controlled phase I trial of safety, pharmacokinetics, pharmacodynamics and acceptability of tenofovir and tenofovir plus levonorgestrel vaginal rings in women. PLoS One 2018;13:e0199778.
  2. Marrazzo JM, Ramjee G, Richardson BA, et al; VOICE Study Team. Tenofovir-based preexposure prophylaxis for HIV infection among African women. N Engl J Med 2015;372:509-518.