By Rebecca Bowers

EXECUTIVE SUMMARY

In an effort to provide both HIV/AIDS and unintended pregnancy protection, researchers have developed a vaginal ring containing the antiretroviral drug dapivirine and the contraceptive hormone levonorgestrel. Scientists have just released results of an initial clinical trial, noting no safety issues.

  • Despite impressive strides in prevention and treatment, AIDS-related illnesses remain the leading cause of death worldwide among women of reproductive age (ages 15-49).
  • U.S. and global regulatory approval is being sought for a 25 mg dapivirine-only vaginal ring. If it is approved, the monthly ring would be the first biomedical HIV prevention method developed specifically for women.

Despite impressive strides in prevention and treatment, AIDS-related illnesses remain the leading cause of death worldwide among women of reproductive age (ages 15-49).1

In an effort to provide both HIV/AIDS and unintended pregnancy protection, researchers have developed a vaginal ring containing the antiretroviral drug dapivirine and the contraceptive hormone levonorgestrel. Scientists have just released results of an initial clinical trial, noting no safety issues.2 (Contraceptive Technology Update reported on the start of this research in the August 2017 article, “Dual-purpose Vaginal Ring Moves to Clinical Trial,” at https://bit.ly/2B4V1rP.) What are the next steps for research?

In the initial trial, conducted at Magee-Womens Hospital in Pittsburgh and the University of Alabama at Birmingham, women used the device for 14 days to allow researchers to assess its safety, as well as to measure uptake of its two drugs. The ring under study contains 200 mg of dapivirine and 320 mg of levonorgestrel. Based on the positive results, researchers are launching a second Phase I trial, in which participants will use the device for 90 days.

With the start of a second study underway, scientists are closer to potentially offering an easy-to-use product with effective and long-acting protection against HIV and unintended pregnancy, said Sharon Achilles, MD, PhD, 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, in a press statement. Achilles serves as protocol chair for the study, a joint effort of the International Partnership for Microbicides (IPM), a nonprofit research group based in Silver Spring, MD, and the U.S. National Institutes of Health-funded Microbicide Trials Network (MTN), based at Magee-Womens Research Institute and the University of Pittsburgh.

“We believe in the promise of multipurpose prevention and [the] results of the first study of the three-month dapivirine-contraceptive ring are welcome progress toward meeting women’s overlapping sexual and reproductive health needs,” states Zeda Rosenberg, ScD, IPM founder and chief executive officer.

Progress in the Pipeline

The IPM 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. Such a device would provide a prevention option besides oral preexposure prophylaxis (PrEP), which consists of the anti-HIV drugs emtricitabine and tenofovir disoproxil fumarate (Truvada). Truvada is the only medication currently approved for HIV PrEP; oral PrEP is being rolled out in many countries for HIV prevention.

In 2016, researchers with MTN and IPM reported the results of two Phase III trials assessing the efficacy of the monthly ring. The findings indicated it was effective in preventing HIV infection. The results suggested that the overall risk of HIV infection was reduced by about 30% in the two studies. Increased levels of protection were noted in women who used the ring with the most regularity.3,4 The two trials involved 4,588 women in Malawi, Uganda, South Africa, and Zimbabwe countries where rates of HIV infection in women remain among the highest in the world. (Contraceptive Technology Update reported on the research; see the May 2016 article, “Two Studies Show Monthly Vaginal Ring Protects Women Against HIV,” http://bit.ly/2twpOHi.)

At the recent 2018 HIV Research for Prevention conference in Madrid, researchers reported minimal risk of drug resistance with use of the dapivirine ring.5 Scientists used both standard genotyping and next-generation sequencing to examine plasma samples from women who acquired HIV during participation in the ASPIRE Phase III trial. Results indicate that among women who acquired HIV in the trial, relatively few had evidence of resistant virus, particularly virus resistant to non-nucleoside reverse transcriptase inhibitors (NNRTIs).5 Dapivirine is classified as an NNRTI.

“We looked pretty hard, using the most sensitive tests that can detect genetic changes in thousands of individual viruses from a single infected person,” says Urvi Parikh, PhD, associate director of the Microbicide Trials Network Laboratory Center Virology and Pharmacodynamics Core at the University of Pittsburgh. “In this study, we found that the risk of dapivirine-related resistance in someone using the dapivirine ring was the same as the risk in someone who wasn’t using the ring.”

REFERENCES

  1. UNAIDS. Global AIDS Monitoring 2017: Indicators for Monitoring the 2016 United Nations Political Declaration on HIV and AIDS. Geneva: UNAIDS; 2017.
  2. Achilles S. Safety and pharmaco-kinetics of dapivirine and levonorgestrel vaginal rings for multipurpose prevention of HIV and pregnancy. Presented at the HIV Research for Prevention conference. Madrid; October 2018.
  3. Nel A, van Niekerk N, Kapiga S, et al; Ring Study Team. Safety and efficacy of a dapivirine vaginal ring for HIV prevention in women. N Engl J Med 2016;375:2133-2143.
  4. Baeten JM, Palanee-Phillips T, Brown ER, et al; MTN-020–ASPIRE Study Team. Use of a vaginal ring containing dapivirine for HIV-1 prevention in women. N Engl J Med 2016;375:2121-2132.
  5. Parikh U. Sensitive next-generation sequencing of HIV-1 from seroconverters in the MTN-020/ASPIRE dapivirine vaginal ring study. Presented at the HIV Research for Prevention conference. Madrid; October 2018.